Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Individuals

NCT04368728 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: C45910012020-002641-42
• Study Type: interventional
• Target: 46,969
• Locations: 6 countries
• Sites: 175

Brief Summary

This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 3 different SARS-CoV-2 RNA vaccine candidates against COVID-19 and the efficacy of 1 candidate:

• As a 2-dose (separated by 21 days) schedule;
• At various different dose levels in Phase 1;
• As a booster;
• In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age \[stratified as 12-15, 16-55 or \>55 years of age\]). The candidate selected for efficacy evaluation in Phase 2/3 is BNT162b2 at a dose of 30 µg. Participants who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study. In order to describe the boostability of BNT162, and potential heterologous protection against emerging SARS-CoV-2 VOCs, an additional dose of BNT162b2 at 30 µg will be given to Phase 1 participants approximately 6 to 12 months after their second dose of BNT162b1 or BNT162b2. This will provide an early assessment of the safety of a third dose of BNT162, as well as its immunogenicity. The assessment of boostability will be further expanded in a subset of Phase 3 participants at selected sites in the US who will receive a third dose of BNT162b2 at 30 µg or a third and potentially a fourth dose of prototype BNT162b2VOC at 30 µg (BNT162b2s01, based upon the South African variant and hereafter referred to as BNT162b2SA). A further subset of Phase 3 participants will receive a third, lower, dose of BNT162b2 at 5 or 10 µg. To further describe potential homologous and heterologous protection against emerging SARS-CoV-2 VOCs, a new cohort of participants will be enrolled who are COVID-19 vaccine-naïve (ie, BNT162b2-naïve) and have not experienced COVID-19. They will receive BNT162b2SA given as a 2-dose series, separated by 21 days. To reflect current and anticipated recommendations for COVID 19 vaccine boosters, participants in C4591001 who meet specified recommendations and have not already received one, will be offered a third dose of BNT162b2 after their second dose of BNT162.

Conditions

SARS-CoV-2 Infection; COVID-19

Keywords

COVID-19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine

Outcome Measures

Primary Outcomes (64)

• Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Phase 1

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than \[\>\] 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 days after Dose 1

• Percentage of Participants With Local Reactions Within 7 Days After Dose 2: Phase 1

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 days after Dose 2

• Percentage of Participants With Systemic Events Within 7 Days After Dose 1: Phase 1

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 hours\[h\]), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 days after Dose 1

• Percentage of Participants With Systemic Events Within 7 Days After Dose 2: Phase 1

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 days after Dose 2

• Percentage of Participants Reporting Adverse Events From Dose 1 to 1 Month After Dose 2: Phase 1

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For BNT162b1 100 mcg, participants received one dose of 100 mcg, followed by one dose of 10 mcg.

  From Dose 1 to 1 Month After Dose 2

• Percentage of Participants Reporting Serious Adverse Events From Dose 1 to 6 Months After Dose 2: Phase 1

  An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. For BNT162b1 100 mcg, participants received one dose of 100 mcg, followed by one dose of 10 mcg.

  From Dose 1 to 6 Months After Dose 2

• Percentage of Participants With Abnormalities in Hematology Parameters 1 Day After Dose 1: Phase 1

  Hematology parameters that were assessed included hemoglobin, hematocrit, erythrocytes, Ery. mean corpuscular volume, Ery. mean corpuscular hemoglobin, Ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Abnormal parameters were determined by following criteria: Hemoglobin : \<0.8x lower limit of normal (LLN), Hematocrit : \<0.8x LLN, Erythrocytes : \<0.8x LLN, Ery. Mean Corpuscular Volume: \<0.9x LLN, Ery. Mean Corpuscular Hemoglobin : \<0.9x LLN Ery. Mean Corpuscular HGB Concentration : \<0.9x LLN, Platelets : \<0.5x LLN, Leukocytes : \<0.6x LLN, Lymphocytes : \<0.8x LLN, Neutrophils : \<0.8x LLN, Basophils: \>1.2x upper limit of normal (ULN), Eosinophils \>1.2x ULN, Monocytes \>1.2x ULN. Only parameters with abnormal values were reported in this outcome measure.

  1 Day After Dose 1

• Percentage of Participants With Abnormalities in Hematology Parameters 7 Days After Dose 1: Phase 1

  Hematology parameters that were assessed included hemoglobin, hematocrit, erythrocytes, Ery. mean corpuscular volume, Ery. mean corpuscular hemoglobin, Ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Abnormal parameters were determined by following criteria: Hemoglobin : \<0.8x LLN, Hematocrit : \<0.8x LLN, Erythrocytes : \<0.8x LLN, Ery. Mean Corpuscular Volume: \<0.9x LLN, Ery. Mean Corpuscular Hemoglobin : \<0.9x LLN Ery. Mean Corpuscular HGB Concentration : \<0.9x LLN, Platelets : \<0.5x LLN, Leukocytes : \<0.6x LLN, Lymphocytes : \<0.8x LLN, Neutrophils : \<0.8x LLN, Basophils: \>1.2x ULN, Eosinophils \>1.2x ULN, Monocytes \>1.2x ULN. Only parameters with abnormal values were reported in this outcome measure.

  7 Days After Dose 1

• Percentage of Participants With Abnormalities in Hematology Parameters Before Dose 2: Phase 1

  Hematology parameters that were assessed included hemoglobin, hematocrit, erythrocytes, Ery. mean corpuscular volume, Ery. mean corpuscular hemoglobin, Ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Abnormal parameters were determined by following criteria: Hemoglobin : \<0.8x LLN, Hematocrit : \<0.8x LLN, Erythrocytes : \<0.8x LLN, Ery. Mean Corpuscular Volume: \<0.9x LLN, Ery. Mean Corpuscular Hemoglobin : \<0.9x LLN Ery. Mean Corpuscular HGB Concentration : \<0.9x LLN, Platelets : \<0.5x LLN, Leukocytes : \<0.6x LLN, Lymphocytes : \<0.8x LLN, Neutrophils : \<0.8x LLN, Basophils: \>1.2x ULN, Eosinophils \>1.2x ULN, Monocytes \>1.2x ULN. Only parameters with abnormal values were reported in this outcome measure.

  Before Dose 2

• Percentage of Participants With Abnormalities in Hematology Parameters 7 Days After Dose 2: Phase 1

  Hematology parameters that were assessed included hemoglobin, hematocrit, erythrocytes, Ery. mean corpuscular volume, Ery. mean corpuscular hemoglobin, Ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Abnormal parameters were determined by following criteria: Hemoglobin : \<0.8x LLN, Hematocrit : \<0.8x LLN, Erythrocytes : \<0.8x LLN, Ery. Mean Corpuscular Volume: \<0.9x LLN, Ery. Mean Corpuscular Hemoglobin : \<0.9x LLN Ery. Mean Corpuscular HGB Concentration : \<0.9x LLN, Platelets : \<0.5x LLN, Leukocytes : \<0.6x LLN, Lymphocytes : \<0.8x LLN, Neutrophils : \<0.8x LLN, Basophils: \>1.2x ULN, Eosinophils \>1.2x ULN, Monocytes \>1.2x ULN. Only parameters with abnormal values were reported in this outcome measure.

  7 Days After Dose 2

• Percentage of Participants With Abnormalities in Chemistry Parameters 1 Day After Dose 1: Phase 1

  Chemistry parameters that were assessed included bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea nitrogen, creatinine. Abnormal parameters were determined by following criteria: bilirubin: \>1.5x ULN, AST: \>3.0x ULN, ALT: \>3.0x ULN, ALP: \>3.0x ULN, urea nitrogen: \>1.3x ULN, creatinine: \>1.3x ULN. Abnormal values reported for this outcome measure are for bilirubin.

  1 Day After Dose 1

• Percentage of Participants With Abnormalities in Chemistry Parameters 7 Days After Dose 1: Phase 1

  Chemistry parameters that were assessed included bilirubin, AST, ALT, ALP, urea nitrogen, creatinine. Abnormal parameters were determined by following criteria: bilirubin: \>1.5x ULN, AST: \>3.0x ULN, ALT: \>3.0x ULN, ALP: \>3.0x ULN, urea nitrogen: \>1.3x ULN, creatinine: \>1.3x ULN. Abnormal values reported for this outcome measure are for bilirubin.

  7 Days After Dose 1

• Percentage of Participants With Abnormalities in Chemistry Parameters Before Dose 2: Phase 1

  Chemistry parameters that were assessed included bilirubin, AST, ALT, ALP, urea nitrogen, creatinine. Abnormal parameters were determined by following criteria: bilirubin: \>1.5x ULN, AST: \>3.0x ULN, ALT: \>3.0x ULN, ALP: \>3.0x ULN, urea nitrogen: \>1.3x ULN, creatinine: \>1.3x ULN. Abnormal values reported for this outcome measure are for bilirubin.

  Before Dose 2

• Percentage of Participants With Abnormalities in Chemistry Parameters 7 Days After Dose 2: Phase 1

  Chemistry parameters that were assessed included bilirubin, AST, ALT, ALP, urea nitrogen, creatinine. Abnormal parameters were determined by following criteria: bilirubin: \>1.5x ULN, AST: \>3.0x ULN, ALT: \>3.0x ULN, ALP: \>3.0x ULN, urea nitrogen: \>1.3x ULN, creatinine: \>1.3x ULN. Abnormal values reported for this outcome measure are for bilirubin.

  7 Days After Dose 2

• Percentage of Participants With Grade Shift in Hematology Parameters 1 Day After Dose 1: Phase 1

  Percentage of participants with grade shift in hematology parameters reported in this outcome measure. Grade(G)1: Mild, G2:Moderate, G3:Severe, G4:potentially life threatening. Hemoglobin(Female): G1: 11.0 - 12.0grams per deciliter(g/dL), G2: 9.5 - 10.9, G3: 8.0 - 9.4, G4: \<8.0. Hemoglobin(Male): G1: 12.5 - 13.5, G2: 10.5 - 12.4, G3: 8.5 - 10.4, G4: \<8.5. WBC decrease(cells/mm3):G1: 2,500 - 3,500, G2: 1,500 - 2,499, G3: 1,000 - 1,499, G4: \<1,000 Lymphocytes decrease(cells/mm3): G1: 750 - 1,000, G2: 500 - 749, G3: 250 - 499, G4: \<250. Eosinophils(cells/mm3):G1: 650 - 1500, G2: 1501 - 5000, G3: \>5000, G4:Hypereosinophilic. Platelets decreased(cells/mm3): G1: 125,000 - 140,000, G2: 100,000 - 124,000, G3: 25,000 - 99,000, G4: \<25,000. Urea Nitrogen (mg/dl): G1: 23-26; G2:27-31; G3: \>31; G4: requires dialysis. Only parameters where grade shift was observed were reported.

  1 Day After Dose 1

• Percentage of Participants With Grade Shift in Hematology Parameters 7 Days After Dose 1: Phase 1

  Percentage of participants with grade shift in hematology parameters reported in this outcome measure. Grade(G)1: Mild, G2:Moderate, G3:Severe, G4:potentially life threatening. Hemoglobin(Female): G1: 11.0 - 12.0grams per deciliter(g/dL), G2: 9.5 - 10.9, G3: 8.0 - 9.4, G4: \<8.0. Hemoglobin(Male): G1: 12.5 - 13.5, G2: 10.5 - 12.4, G3: 8.5 - 10.4, G4: \<8.5. WBC decrease(cells/mm3):G1: 2,500 - 3,500, G2: 1,500 - 2,499, G3: 1,000 - 1,499, G4: \<1,000 Lymphocytes decrease(cells/mm3): G1: 750 - 1,000, G2: 500 - 749, G3: 250 - 499, G4: \<250. Eosinophils(cells/mm3):G1: 650 - 1500, G2: 1501 - 5000, G3: \>5000, G4:Hypereosinophilic. Platelets decreased(cells/mm3): G1: 125,000 - 140,000, G2: 100,000 - 124,000, G3: 25,000 - 99,000, G4: \<25,000. Urea Nitrogen (mg/dl): G1: 23-26; G2:27-31; G3: \>31; G4: requires dialysis. Only parameters where grade shift was observed were reported.

  7 Days After Dose 1

• Percentage of Participants With Grade Shift in Hematology Parameters Before Dose 2: Phase 1

  Percentage of participants with grade shift in hematology parameters reported in this outcome measure. Grade(G)1: Mild, G2:Moderate, G3:Severe, G4:potentially life threatening. Hemoglobin(Female): G1: 11.0 - 12.0grams per deciliter(g/dL), G2: 9.5 - 10.9, G3: 8.0 - 9.4, G4: \<8.0. Hemoglobin(Male): G1: 12.5 - 13.5, G2: 10.5 - 12.4, G3: 8.5 - 10.4, G4: \<8.5. WBC decrease(cells/mm3):G1: 2,500 - 3,500, G2: 1,500 - 2,499, G3: 1,000 - 1,499, G4: \<1,000 Lymphocytes decrease(cells/mm3): G1: 750 - 1,000, G2: 500 - 749, G3: 250 - 499, G4: \<250. Eosinophils(cells/mm3):G1: 650 - 1500, G2: 1501 - 5000, G3: \>5000, G4:Hypereosinophilic. Platelets decreased(cells/mm3): G1: 125,000 - 140,000, G2: 100,000 - 124,000, G3: 25,000 - 99,000, G4: \<25,000. Urea Nitrogen (mg/dl): G1: 23-26; G2:27-31; G3: \>31; G4: requires dialysis. Only parameters where grade shift was observed were reported.

  Before Dose 2

• Percentage of Participants With Grade Shift in Hematology Parameters 7 Days After Dose 2: Phase 1

  Percentage of participants with grade shift in hematology parameters reported in this outcome measure. Grade(G)1: Mild, G2:Moderate, G3:Severe, G4:potentially life threatening. Hemoglobin(Female): G1: 11.0 - 12.0grams per deciliter(g/dL), G2: 9.5 - 10.9, G3: 8.0 - 9.4, G4: \<8.0. Hemoglobin(Male): G1: 12.5 - 13.5, G2: 10.5 - 12.4, G3: 8.5 - 10.4, G4: \<8.5. WBC decrease(cells/mm3):G1: 2,500 - 3,500, G2: 1,500 - 2,499, G3: 1,000 - 1,499, G4: \<1,000 Lymphocytes decrease(cells/mm3): G1: 750 - 1,000, G2: 500 - 749, G3: 250 - 499, G4: \<250. Eosinophils(cells/mm3):G1: 650 - 1500, G2: 1501 - 5000, G3: \>5000, G4:Hypereosinophilic. Platelets decreased(cells/mm3): G1: 125,000 - 140,000, G2: 100,000 - 124,000, G3: 25,000 - 99,000, G4: \<25,000. Urea Nitrogen (mg/dl): G1: 23-26; G2:27-31; G3: \>31; G4: requires dialysis. Only parameters where grade shift was observed were reported.

  7 Days After Dose 2

• Percentage of Participants With Grade Shift in Chemistry Parameters 1 Day After Dose 1: Phase 1

  Percentage of participants with grade shift in chemistry were reported in this outcome measure. G1: Mild, G2: Moderate, G3: Severe, G4: potentially life threatening. BUN(milligram per deciliter \[mg/dL\]): G1: 23 - 26, G2: 27 - 31, G3: \>31, G4: required dialysis. Creatinine(mg/dL): G1: 1.5 - 1.7, G2: 1.8 - 2.0, G3: 2.1 - 2.5, G4: \> 2.5 or required dialysis. Alkaline phosphate(increase by factor): G1: 1.1 - 2.0 x ULN G2: 2.1 - 3.0 x ULN G3: 3.1 -10 x ULN, G4: \>10 x ULN. Liver function tests(ALT, AST increase by factor): G1: 1.1 - 2.5 x ULN G2: 2.6 - 5.0 x ULN G3: 5.1 - 10 x ULN, G4: \>10 x ULN. Bilirubin(when accompanied by any increase in liver function test - increase by factor): G1: 1.1 - 1.25 x ULN G2: 1.26 - 1.5 x ULN G3: 1.51 - 1.75 x ULN, G4: \>1.75 x ULN. Bilirubin(when liver function test is normal - increase by factor): G1: 1.1 - 1.5 x ULN, G2: 1.6 - 2.0 x ULN, G3: 2.0 - 3.0 x ULN, G4: \>3.0 x ULN. Only parameters where grade shift was observed were reported.

  1 Day After Dose 1

• Percentage of Participants With Grade Shift in Chemistry Parameters 7 Days After Dose 1: Phase 1

  Percentage of participants with grade shift in chemistry were reported in this outcome measure. G1: Mild, G2: Moderate, G3: Severe, G4: potentially life threatening. BUN(mg/dL): G1: 23 - 26, G2: 27 - 31, G3: \>31, G4: required dialysis. Creatinine(mg/dL): G1: 1.5 - 1.7, G2: 1.8 - 2.0, G3: 2.1 - 2.5, G4: \> 2.5 or required dialysis. Alkaline phosphate(increase by factor): G1: 1.1 - 2.0 x ULN G2: 2.1 - 3.0 x ULN G3: 3.1 -10 x ULN, G4: \>10 x ULN. Liver function tests(ALT, AST increase by factor): G1: 1.1 - 2.5 x ULN G2: 2.6 - 5.0 x ULN G3: 5.1 - 10 x ULN, G4: \>10 x ULN. Bilirubin(when accompanied by any increase in liver function test - increase by factor): G1: 1.1 - 1.25 x ULN G2: 1.26 - 1.5 x ULN G3: 1.51 - 1.75 x ULN, G4: \>1.75 x ULN. Bilirubin(when liver function test is normal - increase by factor): G1: 1.1 - 1.5 x ULN, G2: 1.6 - 2.0 x ULN, G3: 2.0 - 3.0 x ULN, G4: \>3.0 x ULN. Only parameters where grade shift was observed were reported.

  7 Days After Dose 1

• Percentage of Participants With Grade Shift in Chemistry Parameters Before Dose 2: Phase 1

  Percentage of participants with grade shift in chemistry were reported in this outcome measure. G1: Mild, G2: Moderate, G3: Severe, G4: potentially life threatening. BUN(mg/dL): G1: 23 - 26, G2: 27 - 31, G3: \>31, G4: required dialysis. Creatinine(mg/dL): G1: 1.5 - 1.7, G2: 1.8 - 2.0, G3: 2.1 - 2.5, G4: \> 2.5 or required dialysis. Alkaline phosphate(increase by factor): G1: 1.1 - 2.0 x ULN G2: 2.1 - 3.0 x ULN G3: 3.1 -10 x ULN, G4: \>10 x ULN. Liver function tests(ALT, AST increase by factor): G1: 1.1 - 2.5 x ULN G2: 2.6 - 5.0 x ULN G3: 5.1 - 10 x ULN, G4: \>10 x ULN. Bilirubin(when accompanied by any increase in liver function test - increase by factor): G1: 1.1 - 1.25 x ULN G2: 1.26 - 1.5 x ULN G3: 1.51 - 1.75 x ULN, G4: \>1.75 x ULN. Bilirubin(when liver function test is normal - increase by factor): G1: 1.1 - 1.5 x ULN, G2: 1.6 - 2.0 x ULN, G3: 2.0 - 3.0 x ULN, G4: \>3.0 x ULN. Only parameters where grade shift was observed were reported.

  Before Dose 2

• Percentage of Participants With Grade Shift in Chemistry Parameters 7 Days After Dose 2: Phase 1

  Percentage of participants with grade shift in chemistry were reported in this outcome measure. G1: Mild, G2: Moderate, G3: Severe, G4: potentially life threatening. BUN(mg/dL): G1: 23 - 26, G2: 27 - 31, G3: \>31, G4: required dialysis. Creatinine(mg/dL): G1: 1.5 - 1.7, G2: 1.8 - 2.0, G3: 2.1 - 2.5, G4: \> 2.5 or required dialysis. Alkaline phosphate(increase by factor): G1: 1.1 - 2.0 x ULN G2: 2.1 - 3.0 x ULN G3: 3.1 -10 x ULN, G4: \>10 x ULN. Liver function tests(ALT, AST increase by factor): G1: 1.1 - 2.5 x ULN G2: 2.6 - 5.0 x ULN G3: 5.1 - 10 x ULN, G4: \>10 x ULN. Bilirubin(when accompanied by any increase in liver function test - increase by factor): G1: 1.1 - 1.25 x ULN G2: 1.26 - 1.5 x ULN G3: 1.51 - 1.75 x ULN, G4: \>1.75 x ULN. Bilirubin(when liver function test is normal - increase by factor): G1: 1.1 - 1.5 x ULN, G2: 1.6 - 2.0 x ULN, G3: 2.0 - 3.0 x ULN, G4: \>3.0 x ULN. Only parameters where grade shift was observed were reported.

  7 Days After Dose 2

• Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Phase 2/3

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants or parents/legal guardians in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 Days after Dose 1

• Percentage of Participants With Local Reactions Within 7 Days After Dose 2: Phase 2/3

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants or parents/legal guardians in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 Days after Dose 2

• Percentage of Participants With Systemic Events Within 7 Days After Dose 1: Phase 2/3

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 Days after Dose 1

• Percentage of Participants With Systemic Events Within 7 Days After Dose 2: Phase 2/3

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 Days after Dose 2

• Percentage of Participants Reporting Adverse Events From Dose 1 to 1 Month After Dose 2: Phase 2/3

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. HIV positive participants were excluded from this analysis.

  From Dose 1 to 1 Month After Dose 2

• Percentage of Participants Reporting Serious Adverse Events From Dose 1 to 6 Months After Dose 2: Phase 2/3

  An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. HIV positive participants were excluded from this analysis.

  From Dose 1 to 6 Months After Dose 2

• Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Phase 2

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 Days after Dose 1

• Percentage of Participants With Local Reactions Within 7 Days After Dose 2: Phase 2

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain).

  Within 7 Days after Dose 2

• Percentage of Participants With Systemic Events Within 7 Days After Dose 1: Phase 2

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 Days after Dose 1

• Percentage of Participants With Systemic Events Within 7 Days After Dose 2: Phase 2

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization).

  Within 7 Days After Dose 2

• Percentage of Participants Reporting Adverse Events From Dose 1 to 7 Days After Dose 2: Phase 2

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  From Dose 1 to 7 Days After Dose 2

• Percentage of Participants Reporting Serious Adverse Events From Dose 1 to 7 Days After Dose 2: Phase 2

  A SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events.

  From Dose 1 to 7 Days After Dose 2

• Percentage of Participants With Local Reactions Within 7 Days After Booster Dose: BNT162b2 Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants or parents/legal guardians in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded.

  Within 7 Days After Booster Dose

• Percentage of Participants With Systemic Events Within 7 Days After Booster Dose 1: BNT162b2 Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants were excluded.

  Within 7 Days After Booster Dose

• Percentage of Participants Reporting Adverse Events From First Booster Dose to 1 Month After Booster Dose: BNT162b2 Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. HIV positive participants were excluded.

  From First Booster Dose to 1 Month After Booster Dose

• Percentage of Participants Reporting Serious Adverse Events From First Booster Dose to 6 Months After Booster Dose: BNT162b2 Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose

  A SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. HIV positive participants were excluded.

  From First Booster Dose to 6 Months After Booster Dose

• Percentage of Participants With Local Reactions Within 7 Days After Booster Dose 1: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded from this analysis.

  Within 7 Days After Booster Dose 1

• Percentage of Participants With Local Reactions Within 7 Days After Booster Dose 2: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded from this analysis.

  Within 7 Days after Booster Dose 2

• Percentage of Participants With Systemic Events Within 7 Days After Booster Dose 1: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants excluded.

  Within 7 Days After Booster Dose 1

• Percentage of Participants With Systemic Events Within 7 Days After Booster Dose 2: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants excluded.

  Within 7 Days After Booster Dose 2

• Percentage of Participants Reporting Adverse Events From First Booster Dose to 1 Month After Second Booster Dose: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. HIV positive participants were excluded.

  From First Booster Dose to 1 Month After Second Booster Dose

• Percentage of Participants Reporting Serious Adverse Events From First Booster Dose to 5 Months After Second Booster Dose: BNT162b2 Experienced Participants Assigned to Receive 2 Booster Doses of BNT162b2SA

  An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. HIV positive participants were excluded.

  From First Booster Dose to 5 Months After Second Booster Dose

• Percentage of Participants With Local Reactions Within 7 Days After Dose 1: BNT162b2 Naive Participants Who Were Enrolled to Receive BNT162b2SA

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded.

  Within 7 Days After Dose 1

• Percentage of Participants With Local Reactions Within 7 Days After Dose 2: BNT162b2 Naive Participants Who Were Enrolled to Receive BNT162b2SA

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded.

  Within 7 Days After Dose 2

• Percentage of Participants With Systemic Events Within 7 Days After Dose 1: BNT162b2 Naive Participants Who Were Enrolled to Receive BNT162b2SA

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants were excluded.

  Within 7 Days After Dose 1

• Percentage of Participants With Systemic Events Within 7 Days After Dose 2: BNT162b2 Naive Participants Who Were Enrolled to Receive BNT162b2SA

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants were excluded.

  Within 7 Days After Dose 2

• Percentage of Participants Reporting Adverse Events From Dose 1 to 1 Month After Dose 2: BNT162b2-Naïve Participants Who Were Enrolled to Receive BNT162b2SA

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. HIV positive participants were excluded.

  From Dose 1 Through 1 Month After Dose 2

• Percentage of Participants Reporting Serious Adverse Events From Dose 1 to 6 Months After Dose 2: BNT162b2-Naïve Participants Who Were Enrolled to Receive BNT162b2SA

  A SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. HIV positive participants were excluded.

  From Dose 1 to 6 Months After Dose 2

• Percentage of Participants With Local Reactions Within 7 Days After Booster Dose: BNT162b2-Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose of BNT162b2 (Lower Dose)

  Local reactions included redness, swelling and, pain at the injection site, recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (\> 2.0 to 5.0 cm), moderate (\> 5.0 to 10.0 cm), severe (\>10.0 cm) and Grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity) and Grade 4 (emergency room visit or hospitalization for severe pain). HIV positive participants were excluded.

  Within 7 days After Booster Dose

• Percentage of Participants With Systemic Events Within 7 Days After Booster Dose: BNT162b2-Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose of BNT162b2 (Lower Dose)

  Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain recorded by participants or parents/legal guardians of participants using e-diary. Fever=temperature \>=38.0 deg C categorized as \>=38.0 to 38.4, \>38.4 to 38.9, \>38.9 to 40.0 and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain graded as mild (does not interfere with activity), moderate (some interference with activity), severe (prevents daily routine activity), Grade 4 (Emergency room visit/hospitalization). Vomiting: mild (1-2 times in 24 h), moderate (\>2 times in 24 h), severe (requires IV hydration), Grade 4 (emergency room visit/hospitalization for hypotensive shock). Diarrhea: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24 h), severe (\>=6 loose stools in 24 h) and Grade 4 (emergency room visit/hospitalization). HIV positive participants were excluded.

  Within 7 days After Booster Dose

• Percentage of Participants Reporting Adverse Events From Booster Dose to 1 Month After Booster Dose: BNT162b2-Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose of BNT162b2 (Lower Dose)

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. HIV positive participants were excluded.

  From Booster Dose to 1 Months After Booster Dose

• Percentage of Participants Reporting Serious Adverse Events From Booster Dose to 6 Months After Booster Dose: BNT162b2-Experienced Participants Who Were Rerandomized to Receive 1 Booster Dose of BNT162b2 (Lower Dose)

  A SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. HIV positive participants were excluded.

  From Booster Dose to 6 Months after Booster Dose

• COVID-19 Incidence Based on Central Laboratory or Locally Confirmed Nucleic Acid Amplification Test (NAAT) in Participants Without Serological or Virological Evidence: Phase 2/3

  Occurrences of first COVID-19 infection in participants followed up based on central laboratory or locally confirmed NAAT in participants, without serological or virological evidence of prior SARS-CoV-2 infection were reported in this outcome measure. HIV positive participants were excluded from this analysis.

  From 7 days after Dose 2 (Surveillance time [1000 person-years]: BNT162b2 - 6.247, Placebo - 6.003)

• COVID-19 Incidence Based on Central Laboratory or Locally Confirmed Nucleic Acid Amplification Test (NAAT) in Participants Without Serological or Virological Evidence: Phase 2/3 (Analysis for EUA)

  Occurrences of first COVID-19 infection in participants followed up based on central laboratory or locally confirmed NAAT in participants, without serological or virological evidence of prior SARS-CoV-2 infection (analysis for EUA) were reported in this outcome measure.

  From 7 days after Dose 2 (Surveillance time [1000 person-years]: BNT162b2 - 2.214, Placebo - 2.222)

• COVID-19 Incidence Based on Central Laboratory or Locally Confirmed Nucleic Acid Amplification Test (NAAT) in Participants With or Without Serological or Virological Evidence: Phase 2/3

  Occurrences of first COVID-19 infection in participants followed up based on central laboratory or locally confirmed NAAT in participants, with or without serological or virological evidence of prior SARS-CoV-2 infection were reported in this outcome measure.

  From 7 days after Dose 2 (Surveillance time [1000 person-years]: BNT162b2 - 6.509, Placebo - 6.274)

• COVID-19 Incidence Based on Central Laboratory or Locally Confirmed Nucleic Acid Amplification Test (NAAT) in Participants With or Without Serological or Virological Evidence: Phase 2/3 (Analysis for EUA)

  Occurrences of first COVID-19 infection in participants followed up based on central laboratory or locally confirmed NAAT in participants, with or without serological or virological evidence (analysis for EUA) of prior SARS-CoV-2 infection were reported in this outcome measure. HIV positive participants were excluded from this analysis.

  From 7 days after Dose 2 (Surveillance time [1000 person-years]: BNT162b2 - 2.332, Placebo - 2.345)

• GMR Based on Geometric Mean Titer (N1a) - Comparison of 1 Month After Dose 2 Between Vaccine Groups: BNT162b2-Naïve Participants Without Evidence of Infection (N1a) up to 1 Month After Dose 2: Phase 3

  GMR based on geometric mean titer, comparison of 1 month after dose 2 between vaccine groups: BNT162b2-naive participants without evidence of infection up to 1 month after dose 2 were reported in this outcome measure. HIV positive participants excluded from this analysis.

  1 Month After Dose 2

• Percentage Difference of Participants Achieving Seroresponse Comparison (N1b) of 1 Month After Dose 2 Between Vaccine Groups: BNT162b2-Naïve Participants Without Evidence of Infection up to 1 Month After Dose 2: Phase 3

  Seroresponse was defined as achieving a \>=4-fold rise from baseline (before Dose 1). If the baseline measurement was below the lower limit of quantification (LLOQ), a post vaccination assay result \>=4 × LLOQ was considered a seroresponse. HIV positive participants excluded.

  1 Month After Dose 2

• GMR of Neutralizing Titers (E1a) - Comparison of 1 Month After Booster Dose to 1 Month After Dose 2: BNT162b2-Experienced Participants That Received a Booster Dose of BNT162b2: Phase 3

  GMR based on geometric mean titer, comparison of 1 month after booster dose to 1 month after dose 2 for BNT162b2-experienced participants were reported in this outcome measure. HIV positive participants excluded from this analysis.

  1 Month After Booster Dose to 1 Month After Dose 2

• Percentage Difference of Participants Achieving Seroresponse (E1b) - Comparison of 1 Month After Booster Dose to 1 Month After Dose 2: BNT162b2-Experienced Participants That Received a Booster Dose of BNT162b2: Phase 3

  Percentage difference of participants achieving seroresponse - comparison of 1 month after booster dose to 1 month after Dose 2 BNT162b2-experienced participants without evidence of infection up to 1 month after booster dose who were rerandomized to receive 1 booster dose were reported in this outcome measure. Seroresponse was defined as achieving a \>=4-fold rise from baseline (before Dose 1). If the baseline measurement was below the LLOQ, a postvaccination assay result \>=4 × LLOQ was considered a seroresponse. HIV positive participants excluded.

  1 Month After Booster Dose to 1 Month After Dose 2

• GMR of Neutralizing Titers (E2a) - Comparison of 1 Month After Booster Dose to 1 Month After Dose 2: BNT162b2-Experienced Participants: Phase 3

  GMR of neutralizing titers (E2a) for comparison of 1 month after booster dose to 1 month after dose 2: BNT162b2-experienced participants in Phase 3 were reported in this outcome measure. HIV positive participants were excluded from this analysis.

  1 Month After Booster Dose to 1 Month After Dose 2

• Percentage Difference of Participants Achieving Seroresponse (E2b) - Comparison of 1 Month After Booster Dose to 1 Month After Dose 2: BNT162b2-Experienced Participants: Phase 3

  Percentage difference of participants achieving seroresponse - comparison of 1 month after booster dose to 1 month after Dose 2 BNT162b2-experienced participants without evidence of infection up to 1 month after booster dose who were rerandomized to receive 1 booster dose were reported in this outcome measure. Seroresponse was defined as achieving a \>=4-fold rise from baseline (before Dose 1). If the baseline measurement was below the LLOQ, a postvaccination assay result \>=4 × LLOQ was considered a seroresponse. HIV positive participants excluded.

  1 Month After Booster Dose to 1 Month After Dose 2

Secondary Outcomes (31)

• Geometric Mean Titers (GMTs) of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Titers: Phase 1

  7, 21 days after Dose 1; 7, 14 days and 1, 6 months after Dose 2

• Geometric Mean Concentrations (GMCs) of Severe Acute Respiratory Syndrome Coronavirus 2: S1-binding and RBD-binding IgG Level Assay: Phase 1

  7, 21 days after Dose 1; 7, 14 days and 1, 6 months after Dose 2

• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers: Phase 1

  7, 21 days after Dose 1; 7, 14 days and 1, 6 months after Dose 2

• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 S1-binding and RBD-binding IgG Level Assay: Phase 1

  7, 21 days after Dose 1; 7, 14 days and 1, 6 months after Dose 2

• Percentage of Participants Achieving a >= 4-Fold Rise From Before Vaccination to After Vaccination: Neutralizing Titers: Phase 1

  7, 21 days after Dose 1; 7, 14 days and 1, 6 months after Dose 2

Study Arms (20)

10 µg dose, 18-55 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

20 µg dose, 18-55 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

30 µg dose, 18-55 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

10 µg dose, 65-85 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

20 µg dose, 65-85 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

30 µg dose, 65-85 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1; Biological: BNT162b2

30 µg dose, ≥12 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b2

Placebo, 18-55 years of age

PLACEBO COMPARATOR

Other: Placebo

Placebo, 65-85 years of age

PLACEBO COMPARATOR

Other: Placebo

Placebo, ≥12 years of age

PLACEBO COMPARATOR

Other: Placebo

100 µg dose, 18-55 years of age (2 doses)

EXPERIMENTAL

Biological: BNT162b1

Vaccination of Placebo recipients with BNT162b2 - Stage 1

OTHER

Participants ≥16 years of age who originally received placebo and are eligible for COVID-19 vaccination following any local or national recommendations will be offered the opportunity to receive BNT162b2 as part of the study.

Biological: BNT162b2

Vaccination of placebo recipients with BNT162b2 - Stage 2

OTHER

Participants ≥16 years of age who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study.

Biological: BNT162b2

Booster vaccination of Phase 1 participants with BNT162b2 at a dose of 30 µg

EXPERIMENTAL

Biological: BNT162b2

Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 30 µg

EXPERIMENTAL

Biological: BNT162b2

Booster vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg

EXPERIMENTAL

Biological: BNT162b2SA

Vaccination of BNT162b2-naive participants with BNT162b2SA at a dose of 30 µg

EXPERIMENTAL

Biological: BNT162b2SA

Booster and further vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg

EXPERIMENTAL

Biological: BNT162b2SA

Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 5 µg

EXPERIMENTAL

Biological: BNT162b2

Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 10 µg

EXPERIMENTAL

Biological: BNT162b2

Interventions

BNT162b1 BIOLOGICAL

Intramuscular injection

10 µg dose, 18-55 years of age (2 doses); 10 µg dose, 65-85 years of age (2 doses); 100 µg dose, 18-55 years of age (2 doses); 20 µg dose, 18-55 years of age (2 doses); 20 µg dose, 65-85 years of age (2 doses); 30 µg dose, 18-55 years of age (2 doses); 30 µg dose, 65-85 years of age (2 doses)

BNT162b2 BIOLOGICAL

Intramuscular injection

10 µg dose, 18-55 years of age (2 doses); 10 µg dose, 65-85 years of age (2 doses); 20 µg dose, 18-55 years of age (2 doses); 20 µg dose, 65-85 years of age (2 doses); 30 µg dose, 18-55 years of age (2 doses); 30 µg dose, 65-85 years of age (2 doses); 30 µg dose, ≥12 years of age (2 doses); Booster vaccination of Phase 1 participants with BNT162b2 at a dose of 30 µg; Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 10 µg; Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 30 µg; Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 5 µg; Vaccination of Placebo recipients with BNT162b2 - Stage 1; Vaccination of placebo recipients with BNT162b2 - Stage 2

Placebo OTHER

Intramuscular injection

Placebo, 18-55 years of age; Placebo, 65-85 years of age; Placebo, ≥12 years of age

BNT162b2SA BIOLOGICAL

Intramuscular injection

Booster and further vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg; Booster vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg; Vaccination of BNT162b2-naive participants with BNT162b2SA at a dose of 30 µg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase). For the boostability and protection-against-VOCs subset: Existing participants enrolled to receive a third dose of BNT162b2 at 30 µg or BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at rerandomization.
• Newly enrolled participants enrolled to receive 2 doses of BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at enrollment.
• Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg; male or female participants ≥18 years at rerandomization.
• Note that participants \<18 years of age cannot be enrolled in the EU.
• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
• Participants who, in the judgment of the investigator, are at risk for acquiring COVID-19.
• Boostability and protection-against-VOCs existing participant subset only: Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the protocol-specified window.
• Capable of giving personal signed informed consent

You may not qualify if:

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Receipt of medications intended to prevent COVID 19.
• Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID 19
• Phase 1 only: Individuals at high risk for severe COVID-19, including those with any of the following risk factors:
• Hypertension
• Diabetes mellitus
• Chronic pulmonary disease
• Asthma
• Current vaping or smoking
• History of chronic smoking within the prior year
• BMI \>30 kg/m2
• Anticipating the need for immunosuppressive treatment within the next 6 months
• Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).

Sponsors & Collaborators

• BioNTech SE: lead
• Pfizer: collaborator

Study Sites (175)

North Alabama Research Center, LLC

Athens, Alabama, 35611, United States

Location

Birmingham Clinical Research Unit

Birmingham, Alabama, 35216, United States

Location

Medical Affiliated Research Center

Huntsville, Alabama, 35801, United States

Location

Optimal Research, LLC

Huntsville, Alabama, 35802, United States

Location

Alliance for Multispecialty Research, LLC

Mobile, Alabama, 36608, United States

Location

Chinle Comprehensive Health Care Facility

Chinle, Arizona, 86503, United States

Location

Johns Hopkins Center for American Indian Health

Chinle, Arizona, 86503, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85018, United States

Location

The Pain Center of Arizona

Phoenix, Arizona, 85018, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85023, United States

Location

Alliance for Multispecialty Research, LLC

Tempe, Arizona, 85281, United States

Location

Johns Hopkins Center for American Indian Health

Whiteriver, Arizona, 85941, United States

Location

Whiteriver Indian Hospital - Garrett Building

Whiteriver, Arizona, 85941, United States

Location

Whiteriver Indian Hospital

Whiteriver, Arizona, 85941, United States

Location

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Collaborative Neuroscience Research, LLC. - Investigator Site File Location

Garden Grove, California, 92845, United States

Location

Collaborative Neuroscience Research, LLC

Long Beach, California, 90806, United States

Location

Long Beach Clinical Trials Services Inc.

Long Beach, California, 90806, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Velocity Clinical Research, North Hollywood

North Hollywood, California, 91606, United States

Location

Paradigm Clinical Research Center

Redding, California, 96001, United States

Location

Kaiser Permanente Sacramento

Sacramento, California, 95815, United States

Location

Clinical and Translational Science Center (CTSC) Clinical Research Center (CCRC)

Sacramento, California, 95817, United States

Location

University of California Davis Health

Sacramento, California, 95817, United States

Location

California Research Foundation

San Diego, California, 92123, United States

Location

Kaiser Permanente Santa Clara

Santa Clara, California, 95051, United States

Location

Bayview Research Group

Valley Village, California, 91607, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Lynn Institute of Denver

Aurora, Colorado, 80012, United States

Location

Clinical Research Consulting, LLC

Milford, Connecticut, 06460, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Yale Center for Clinical Investigations (CSRU)

New Haven, Connecticut, 06519, United States

Location

Alliance for Multispecialty Research

Coral Gables, Florida, 33134, United States

Location

DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Fleming Island Center for Clinical Research

Fleming Island, Florida, 32003, United States

Location

Indago Research & Health Center, Inc

Hialeah, Florida, 33012, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

Location

Acevedo Clinical Research Associates

Miami, Florida, 33142, United States

Location

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare

Orlando, Florida, 32801, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Meridian Clinical Research

Savannah, Georgia, 31406, United States

Location

Velocity Clinical Research, Washington DC

Savannah, Georgia, 31406, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Solaris Clinical Research

Meridian, Idaho, 83646, United States

Location

Optimal Research

Peoria, Illinois, 61614, United States

Location

University of Iowa Hospitals & Clinics Investigational Drug Servces

Iowa City, Iowa, 42242, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Velocity Clinical Research, Norfolk

Sioux City, Iowa, 51106, United States

Location

Alliance for Multispecialty Research, LLC

Newton, Kansas, 67114, United States

Location

Alliance for Multispecialty Research, LLC

Wichita, Kansas, 67207, United States

Location

Kentucky Pediatric/ Adult Research

Bardstown, Kentucky, 40004, United States

Location

Benchmark Research

Metairie, Louisiana, 70006, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

LSU Health Sciences Center at Shreveport Clinical Trials Office

Shreveport, Louisiana, 71101, United States

Location

LSUHSC-Shreveport

Shreveport, Louisiana, 71103, United States

Location

Pharmaron CPC, Inc.

Baltimore, Maryland, 21201, United States

Location

University of Maryland Medical Center Investigational Drug Service Pharmacy

Baltimore, Maryland, 21201, United States

Location

University of Maryland, Baltimore, Health Sciences Research Facility III

Baltimore, Maryland, 21201, United States

Location

University of Maryland, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

Michigan Center for Medical Research

Farmington Hills, Michigan, 48334, United States

Location

MedPharmics, LLC

Gulfport, Mississippi, 39503, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, 63141, United States

Location

Bozeman Health Deaconess Hospital dba Bozeman Health Clinical Research

Bozeman, Montana, 59715, United States

Location

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States

Location

Methodist Physicians Clinic / CCT Research

Fremont, Nebraska, 68025, United States

Location

Velocity Clinical Research, Norfolk

Norfolk, Nebraska, 68701, United States

Location

Quality Clinical Research, Inc.

Omaha, Nebraska, 68114, United States

Location

Meridian Clinical Research, LLC

Omaha, Nebraska, 68134, United States

Location

Wake Research-Clinical Research Center of Nevada, LLC

Las Vegas, Nevada, 89106, United States

Location

Amici Clinical Research

Raritan, New Jersey, 08869, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

Gallup Indian Medical Center

Gallup, New Mexico, 87301, United States

Location

Johns Hopkins Center for American Indian Health

Gallup, New Mexico, 87301, United States

Location

Johns Hopkins Center for American Indian Health

Shiprock, New Mexico, 87420, United States

Location

Northern Navajo Medical Center

Shiprock, New Mexico, 87420, United States

Location

Meridian Clinical Research, LLC

Binghamton, New York, 13901, United States

Location

Meridian Clinical Research LLC

Binghamton, New York, 13905, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai - Investigational Drug Service

New York, New York, 10029, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

University of Rochester Medical Center- Kari Steinmetz

Rochester, New York, 14642, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Global Health Research Unit

Syracuse, New York, 13215, United States

Location

Meridian Clinical Research LLC

Vestal, New York, 13850, United States

Location

PMG Research of Raleigh, LLC d/b/a PMG Research of Cary

Cary, North Carolina, 27518, United States

Location

PMG Research of Charlotte LLC

Charlotte, North Carolina, 28209, United States

Location

Duke University - Main Hospital and Clinics

Durham, North Carolina, 27703, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

PMG Research of Hickory, LLC

Hickory, North Carolina, 28601, United States

Location

PMG Research of Raleigh, LLC

Raleigh, North Carolina, 27609, United States

Location

M3 Wake Research, Inc.

Raleigh, North Carolina, 27612, United States

Location

PMG Research of Salisbury, LLC

Salisbury, North Carolina, 28144, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Lillestol Research Llc

Fargo, North Dakota, 58104, United States

Location

Meridian Clinical Research, LLC

Cincinnati, Ohio, 45219, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Meridian Clinical Research LLC

Cincinnati, Ohio, 45246, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

VA Northeast Ohio Healthcare System

Cleveland, Ohio, 44106, United States

Location

Velocity Clinical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43213, United States

Location

Dayton Clinical Research

Dayton, Ohio, 45406, United States

Location

Dayton Clinical Research

Dayton, Ohio, 45409, United States

Location

PriMED Clinical Research

Dayton, Ohio, 45429, United States

Location

Senders Pediatrics

South Euclid, Ohio, 44121, United States

Location

Lynn Institute of Norman

Norman, Oklahoma, 73072, United States

Location

Kaiser Permanente Northwest-Center for Health Research

Portland, Oregon, 97227, United States

Location

Lehigh Valley Health Network/Network Office of Research and Innovation

Allentown, Pennsylvania, 18102, United States

Location

Velocity Clinical Research, Providence

East Greenwich, Rhode Island, 02818, United States

Location

Main Street Physician's Care

Little River, South Carolina, 29566, United States

Location

Main Street Physician's Care

Loris, South Carolina, 29569, United States

Location

Holston Medical Group-Clinical Research

Bristol, Tennessee, 37620, United States

Location

Holston Medical Group

Kingsport, Tennessee, 37660, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37909, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37920, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

Trinity Clinical Research

Tullahoma, Tennessee, 37388, United States

Location

Benchmark Research

Austin, Texas, 78705, United States

Location

Innovo Research - Austin Regional Clinic

Austin, Texas, 78726, United States

Location

Tekton Research, Inc.

Austin, Texas, 78745, United States

Location

North Texas Infectious Diseases Consultants, P.A.

Dallas, Texas, 75246, United States

Location

Ventavia Research Group, LLC

Fort Worth, Texas, 76104, United States

Location

Benchmark Research

Fort Worth, Texas, 76135, United States

Location

Texas Health Resources

Fort Worth, Texas, 76135, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Hany H. Ahmed, MD

Houston, Texas, 77008, United States

Location

Ventavia Research Group, LLC

Houston, Texas, 77008, United States

Location

Texas Center for Drug Development, Inc.

Houston, Texas, 77081, United States

Location

Ventavia Research Group, LLC

Keller, Texas, 76248, United States

Location

SMS Clinical Research, LLC

Mesquite, Texas, 75149, United States

Location

LinQ Research, LLC

Pearland, Texas, 77584, United States

Location

Benchmark Research.

San Angelo, Texas, 76904, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

Martin Diagnostic Clinic

Tomball, Texas, 77375, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic

Salt Lake City, Utah, 84109, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic South

Salt Lake City, Utah, 84121, United States

Location

Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)

Annandale, Virginia, 22003, United States

Location

Infectious Diseases Physicians, LLC

Annandale, Virginia, 22003, United States

Location

Virginia Research Center LLC

Midlothian, Virginia, 23114, United States

Location

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States

Location

Wenatchee Valley Hospital

Wenatchee, Washington, 98801, United States

Location

Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich

CABA, 1426, Argentina

Location

Hospital Santo Antonio/ Associacao Obras Sociais Irma Dulce

Salvador, Estado de Bahia, CEP: 40415-006, Brazil

Location

CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda (Casa Branca)

São Paulo, 04266-010, Brazil

Location

CRS Clinical Research Services Berlin GmbH

Berlin, 13353, Germany

Location

Medizentrum Essen Borbeck

Essen, 45355, Germany

Location

IKF Pneumologie GmbH & Co KG

Frankfurt am Main, 60596, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20359, Germany

Location

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Location

Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher

Stuhr, 28816, Germany

Location

Newtown Clinical Research Centre

Johannesburg, Gauteng, 2113, South Africa

Location

Jongaie Research

Pretoria, Gauteng, 0183, South Africa

Location

Limpopo Clinical Research Initiative

Thabazimbi, Limpopo, 0380, South Africa

Location

Tiervlei Trial Centre, Basement Level, Karl Bremer Hospital

Cape Town, Western Cape, 7530, South Africa

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, 06230, Turkey (Türkiye)

Location

Istanbul Yedikule Gogus Hastaliklari ve Gogus Cerrahisi Egitim Arastirma Hastanesi

Istanbul, 34020, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul Universitesi-Cerrahpasa, Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Medipol Mega Universite Hastanesi

Istanbul, 34214, Turkey (Türkiye)

Location

Acibadem Atakent Hastanesi

Istanbul, 34303, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Sakarya Universitesi Egitim ve Arastirma Hastanesi

Sakarya, 54100, Turkey (Türkiye)

Location

Related Publications (15)

• Zorger AM, Hirsch C, Baumann M, Feldmann M, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with haematological malignancies. Cochrane Database Syst Rev. 2025 May 21;5(5):CD015530. doi: 10.1002/14651858.CD015530.pub2.

  PMID: 40396505 DERIVED

• Hirsch C, Zorger AM, Baumann M, Park YS, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with solid tumours. Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015551. doi: 10.1002/14651858.CD015551.pub2.

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• Pather S, Charpentier N, van den Ouweland F, Rizzi R, Finlayson A, Salisch N, Muik A, Lindemann C, Khanim R, Abduljawad S, Smith ER, Gurwith M, Chen RT; Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG). A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine. Vaccine. 2024 Sep 17;42(22):126165. doi: 10.1016/j.vaccine.2024.126165. Epub 2024 Aug 27.

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• Killeen T, Kermer V, Troxler Saxer R. mRNA vaccine development during the COVID-19 pandemic: a retrospective review from the perspective of the Swiss affiliate of a global biopharmaceutical company. J Pharm Policy Pract. 2023 Nov 27;16(1):158. doi: 10.1186/s40545-023-00652-y.

  PMID: 38012751 DERIVED

• Fraiman J, Erviti J, Jones M, Greenland S, Whelan P, Kaplan RM, Doshi P. Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine. 2022 Sep 22;40(40):5798-5805. doi: 10.1016/j.vaccine.2022.08.036. Epub 2022 Aug 31.

  PMID: 36055877 DERIVED

• Kurhade C, Zou J, Xia H, Liu M, Yang Q, Cutler M, Cooper D, Muik A, Sahin U, Jansen KU, Ren P, Xie X, Swanson KA, Shi PY. Neutralization of Omicron sublineages and Deltacron SARS-CoV-2 by three doses of BNT162b2 vaccine or BA.1 infection. Emerg Microbes Infect. 2022 Dec;11(1):1828-1832. doi: 10.1080/22221751.2022.2099305.

  PMID: 35792746 DERIVED

• Kurhade C, Zou J, Xia H, Cai H, Yang Q, Cutler M, Cooper D, Muik A, Jansen KU, Xie X, Swanson KA, Shi PY. Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine. Nat Commun. 2022 Jun 23;13(1):3602. doi: 10.1038/s41467-022-30681-1.

  PMID: 35739094 DERIVED

• De Santis F, Gubbiotti S. Borrowing historical information for non-inferiority trials on Covid-19 vaccines. Int J Biostat. 2022 Apr 27;19(1):177-189. doi: 10.1515/ijb-2021-0120. eCollection 2023 May 1.

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• Thomas SJ, Perez JL, Lockhart SP, Hariharan S, Kitchin N, Bailey R, Liau K, Lagkadinou E, Tureci O, Sahin U, Xu X, Koury K, Dychter SS, Lu C, Gentile TC, Gruber WC. Efficacy and safety of the BNT162b2 mRNA COVID-19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial. Vaccine. 2022 Mar 1;40(10):1483-1492. doi: 10.1016/j.vaccine.2021.12.046. Epub 2021 Dec 24.

  PMID: 35131133 DERIVED

• Thomas SJ, Moreira ED Jr, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Polack FP, Zerbini C, Bailey R, Swanson KA, Xu X, Roychoudhury S, Koury K, Bouguermouh S, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Yang Q, Liberator P, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Gruber WC, Jansen KU; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. N Engl J Med. 2021 Nov 4;385(19):1761-1773. doi: 10.1056/NEJMoa2110345. Epub 2021 Sep 15.

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• Frenck RW Jr, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, Perez JL, Walter EB, Senders S, Bailey R, Swanson KA, Ma H, Xu X, Koury K, Kalina WV, Cooper D, Jennings T, Brandon DM, Thomas SJ, Tureci O, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021 Jul 15;385(3):239-250. doi: 10.1056/NEJMoa2107456. Epub 2021 May 27.

  PMID: 34043894 DERIVED

• Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M, Kranz LM, Walzer KC, Hein S, Guler A, Loschko J, Maddur MS, Ota-Setlik A, Tompkins K, Cole J, Lui BG, Ziegenhals T, Plaschke A, Eisel D, Dany SC, Fesser S, Erbar S, Bates F, Schneider D, Jesionek B, Sanger B, Wallisch AK, Feuchter Y, Junginger H, Krumm SA, Heinen AP, Adams-Quack P, Schlereth J, Schille S, Kroner C, de la Caridad Guimil Garcia R, Hiller T, Fischer L, Sellers RS, Choudhary S, Gonzalez O, Vascotto F, Gutman MR, Fontenot JA, Hall-Ursone S, Brasky K, Griffor MC, Han S, Su AAH, Lees JA, Nedoma NL, Mashalidis EH, Sahasrabudhe PV, Tan CY, Pavliakova D, Singh G, Fontes-Garfias C, Pride M, Scully IL, Ciolino T, Obregon J, Gazi M, Carrion R Jr, Alfson KJ, Kalina WV, Kaushal D, Shi PY, Klamp T, Rosenbaum C, Kuhn AN, Tureci O, Dormitzer PR, Jansen KU, Sahin U. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature. 2021 Apr;592(7853):283-289. doi: 10.1038/s41586-021-03275-y. Epub 2021 Feb 1.

  PMID: 33524990 DERIVED

• Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10.

  PMID: 33301246 DERIVED

• Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Tureci O, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Sahin U, Gruber WC. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020 Dec 17;383(25):2439-2450. doi: 10.1056/NEJMoa2027906. Epub 2020 Oct 14.

  PMID: 33053279 DERIVED

• Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Tureci O, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Sahin U, Jansen KU. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020 Oct;586(7830):589-593. doi: 10.1038/s41586-020-2639-4. Epub 2020 Aug 12.

  PMID: 32785213 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

BNT162 Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

6131 90840

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 30, 2020
• Study Start: April 29, 2020
• Primary Completion: February 10, 2023
• Study Completion: February 10, 2023
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (4); AR (1); BR (2); DE (6); TU (8); US (154)