Study to Evaluate Safety, Tolerability & Immunogenicity of BNT162b2 in Immunocompromised Participants ≥2 Years

NCT04895982 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: C45910242021-001290-23
• Study Type: interventional
• Target: 124
• Locations: 4 countries
• Sites: 29

Brief Summary

This is a 4 dose study with 124 participants (7 adults ,117 children). Adults are considered to be participants 18 years of age or older. Participants are going to be enrolled based on conditions that make them immunocompromised. Participants are going to be followed up for 6 months after dose 4, and each participant is projected to be on the study for approximately 15 months. This study will be conducted in the United States, Brazil, Germany and Mexico.

Conditions

SARS-CoV-2 Infection, COVID19

Keywords

COVID19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine

Outcome Measures

Primary Outcomes (56)

• Geometric Mean Titers (GMTs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV 2) Neutralizing Titers at 1 Month After Vaccination 3 in Participants Aged >=2 to <5 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided confidence intervals (CIs) were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 3 Evaluable Immunogenicity population (EIP).

  1 Month after Vaccination 3

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 3 in Participants Aged >=5 to <12 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 3 EIP.

  1 Month after Vaccination 3

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 3 in Participants Aged 12 to <18 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 3 EIP.

  1 Month after Vaccination 3

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 3 in Participants Aged >=18 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 3 EIP.

  1 Month after Vaccination 3

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 4 in Participants Aged >=2 to <5 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 4 EIP.

  1 Month after Vaccination 4

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 4 in Participants Aged >=5 to <12 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 4 EIP.

  1 Month after Vaccination 4

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 4 in Participants Aged 12 to <18 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below LLOQ were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 4 EIP.

  1 Month after Vaccination 4

• GMTs of SARS-CoV-2 Neutralizing Titers at 1 Month After Vaccination 4 in Participants Aged >=18 Years Without Serological or Virological Evidence of Past SARS-CoV-2 Infection

  GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution). Assay results below lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. Participants who had no serological or virological evidence (prior to the subsequent blood sample collection) of past SARS-CoV-2 infection (i.e, negative N-binding antibody \[serum\] result at any visit prior to subsequent time point, SARS-CoV-2 not detected by NAAT \[nasal swab\] until prior vaccination, and negative NAAT \[nasal swab\] result at any unscheduled visit prior to subsequent blood sample collection) and had no medical history of COVID-19 were included in the analysis. Analysis was performed in Dose 4 EIP .

  1 Month after Vaccination 4

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=2 to <5 Years

  Local reactions were collected in an electronic diary (e-diary) or during unscheduled clinical assessments from Day 1 to 7 after vaccination 1. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (\>0.5 to 2.0 cm), moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4 (necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room \[ER\] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=5 to <12 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 1.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=12 to <18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 1. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 1. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=2 to <5 Years

  Local reactions collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 2. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate(\>2.0 to 7.0 cm), severe(\>7.0 cm) and Grade 4 (necrosis \[swelling\] or necrosis or exfoliative dermatitis\[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate(interfered with activity), severe(prevented daily activity),Grade 4(ER visit or hospitalization for severe pain at injection site).Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=5 to <12 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 2.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=12 to <18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 2. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 2. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=2 to <5 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 3.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=5 to <12 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 3.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=12 to <18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 3. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate(interfered with activity), severe(prevented daily activity) and Grade 4(ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 3. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=2 to <5 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 4.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=5 to <12 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 4.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (\>0.5 to 2.0 cm),moderate (\>2.0 to 7.0 cm), severe (\>7.0 cm) and Grade 4(necrosis \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=12 to <18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 4. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=18 Years

  Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after vaccination 4. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and 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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Reactions reported as adverse events in case report form within 7 days of study vaccination were also included. Two-sided 95% CI was based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=2 to <5 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 1. Fever was defined as oral temperature \>=38.0 degree C (deg C); categorized as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=5 to <12 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 1. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=12 to <18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 1. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 in Participants Aged >=18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 1. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 1

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=2 to <5 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 2. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=5 to <12 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 2. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=12 to <18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 2. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 2 in Participants Aged >=18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 2. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 2

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=2 to <5 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 3. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=5 to <12 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 3. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=12 to <18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 3. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 in Participants Aged >=18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 3. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 3

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=2 to <5 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 4. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=5 to <12 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 4. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 de, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=12 to <18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 4. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 4 in Participants Aged >=18 Years

  Systemic events were recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after vaccination 4. Fever was defined as oral temperature \>=38.0 deg C; categorised as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity).Vomiting: mild: 1-2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration. Diarrhea: mild: 2-3 loose stools in 24 hours, moderate: 4-5 loose stools in 24 hours, severe: 6 or more loose stools in 24 hours. Grade 4 for all events: ER visit/hospitalization and were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method.

  Day 1 to Day 7 after Vaccination 4

• Percentage of Participants Reporting at Least 1 Adverse Event (AE) After Vaccination 1 to 1 Month After Vaccination 2 in Participants Aged >=2 to <5 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 1 to 1 month after Vaccination 2

• Percentage of Participants Reporting at Least 1 Adverse Event After Vaccination 1 to 1 Month After Vaccination 2 in Participants Aged >=5 to <12 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 1 to 1 month after Vaccination 2

• Percentage of Participants Reporting at Least 1 Adverse Event After Vaccination 1 to 1 Month After Vaccination 2 in Participants Aged >=12 to <18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 1 to 1 month after Vaccination 2

• Percentage of Participants Reporting at Least 1 Adverse Event After Vaccination 1 to 1 Month After Vaccination 2 in Participants Aged >=18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 1 to 1 month after Vaccination 2

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 3 to 1 Month After Vaccination 3 in Participants Aged >=2 to <5 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 3 to 1 month after Vaccination 3

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 3 to 1 Month After Vaccination 3 in Participants Aged >=5 to <12 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 3 to 1 month after Vaccination 3

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 3 to 1 Month After Vaccination 3 in Participants Aged >=12 to <18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 3 to 1 month after Vaccination 3

• Percentage of Participants Reporting at Least 1 Adverse Event After Vaccination 3 to 1 Month After Vaccination 3 in Participants Aged >=18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 3 to 1 month after Vaccination 3

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 4 to 1 Month After Vaccination 4 in Participants Aged >=2 to <5 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 4 to 1 month after Vaccination 4

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 4 to 1 Month After Vaccination 4 in Participants Aged >=5 to <12 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 4 to 1 month after Vaccination 4

• Percentage of Participants Reporting at Least 1 Adverse Event From Vaccination 4 to 1 Month After Vaccination 4 in Participants Aged >=12 to <18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 4 to 1 month after Vaccination 4

• Percentage of Participants Reporting at Least 1 Adverse Event After Vaccination 4 to 1 Month After Vaccination 4 in Participants Aged >=18 Years

  An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs after vaccination 1 to 1 month after vaccination 2 were reported in this outcome measure. Exact 2-sided CI based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

  From Vaccination 4 to 1 month after Vaccination 4

• Percentage of Participants Reporting Serious Adverse Events (SAEs) From Vaccination 1 Through the Duration of the Study in Participants Aged >=2 to <5 Years

  An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, and other situations as medical judgement of investigator. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

  From Vaccination 1 to 6 months after Vaccination 4 (approximately 14 months)

• Percentage of Participants Reporting SAEs From Vaccination 1 Through the Duration of the Study in Participants Aged >=5 to <12 Years

  An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, and other situations as medical judgement of investigator. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

  From Vaccination 1 to 6 months after Vaccination 4 (approximately 14 months)

• Percentage of Participants Reporting SAEs From Vaccination 1 Through the Duration of the Study in Participants Aged >=12 to <18 Years

  An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, and other situations as medical judgement of investigator. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

  From Vaccination 1 to 6 months after Vaccination 4 (approximately 14 months)

• Percentage of Participants Reporting SAEs From Dose 1 Through the Duration of the Study in Participants Aged >=18 Years

  An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, and other situations as medical judgement of investigator. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

  From Vaccination 1 to 6 months after Vaccination 4 (approximately 14 months)

Study Arms (1)

BNT162b2

EXPERIMENTAL

Intramuscular Injection

Biological: BNT162b2

Interventions

BNT162b2 BIOLOGICAL

Intramuscular Injection

BNT162b2

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants who are ≥2 years of age at the time of enrollment (Visit 1).
• Participants or participants' parent(s)/legal guardians, as age appropriate, who sign consent, and are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment (Visit 1).
• Participants or participant's parent(s)/legal guardians, as age appropriate, who are able to be contacted by telephone throughout the study period.
• Female participant of childbearing potential or male participant able to father children who is willing to use a highly effective method of contraception as outlined in this protocol for at least 28 days after the last dose of study intervention if at risk of pregnancy with her/his partner; or female participant not of childbearing potential or male participant not able to father children.
• Participants who are immunocompromised by virtue of the following:
• Having known non-small cell lung cancer (NSCLC) and is ≥18 years of age with at least 1 of the following:
• Who received chemotherapy at least 2 weeks (14 days) before enrollment (or is treatment naïve), and is not expected to receive chemotherapy within at least 2 weeks (14 days) after dose administration; and/or
• Receiving checkpoint inhibitor treatment (programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor) and has undergone at least 1 treatment cycle prior to enrollment (at Visit 1); or
• Receiving targeted drug therapy treatment (epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene tyrosine-protein kinase (ROS1), v-raf murine sarcoma viral oncogene homolog B1 (BRAF),rearranged during transfection (RET),hepatocyte growth factor receptor (MET), neurotrophic tyrosine kinase (NTRK) inhibitors) and has undergone at least 1 treatment cycle prior to enrollment (at Visit 1); or
• Having known chronic lymphocytic leukemia (CLL) and is ≥18 years of age with at least 1 of the following:
• Has asymptomatic disease (eg, Rai stage \<3, Binet stage A or B) and is undergoing observation and does not receive any treatment for CLL; or
• Receiving B-cell inhibitory monoclonal antibody treatment (anti-CD20) and has received at least 3 cycles prior to enrollment; and/or
• Receives a Bruton tyrosine kinase (BTK) inhibitor, phosphoinositide 3-kinase (PI3K) inhibitor, or B-cell lymphoma-2 (BCL-2) inhibitor; or
• Is currently undergoing maintenance hemodialysis treatment secondary to end-stage renal disease and is ≥18 years of age; or

You may not qualify if:

• Past 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, or a past clinical diagnosis of multisystem inflammatory syndrome in children (MIS-C).
• Participants with active graft-vs-host disease (GVHD), transplant rejection, or posttransplant lymphoproliferative disorder (PTLD), or participants who have had treatment for these conditions within 3 months (84 days) prior to study enrollment (Visit 1).
• Participants \<18 years of age whose weight is less than the 5th percentile of age-adjusted ideal body weight.
• 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.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Participant who is pregnant or breastfeeding.
• Participants who may be ineligible because of the number of phlebotomy assessments during this study, in the opinion of the investigator.
• Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.
• Previous vaccination with any coronavirus vaccine.
• Ongoing, or history of, treatment with blood/plasma products or immunoglobulins within 3 months (84 days) prior to Dose 1 or planned receipt of these medications prior to Dose 4.
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• Previous participation in other studies involving study intervention containing lipid nanoparticle (LNPs).
• Participants who are direct descendants (child or grandchild) of investigational site staff members or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Sponsors & Collaborators

• BioNTech SE: lead
• Pfizer: collaborator

Study Sites (29)

Ochsner Clinic Foundation

Jefferson, Louisiana, 70121, United States

Location

Ochsner Medical Center - Jefferson Highway

Jefferson, Louisiana, 70121, United States

Location

Ochsner Clinic Foundation

Kenner, Louisiana, 70065, United States

Location

Ochsner Medical Center Kenner

Kenner, Louisiana, 70065, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Ochsner Medical Center - Jefferson Highway

New Orleans, Louisiana, 70121, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Henry Ford Hospital - Research Pharmacy

Detroit, Michigan, 48202, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45206, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cincinnati Children's Hospital Vaccine Research Center

Cincinnati, Ohio, 45229, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Research Institute: Building Cure

Seattle, Washington, 98101, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90410000, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

GRAACC - Grupo de Apoio ao Adolescente e à Criança com Câncer

São Paulo, 04039-001, Brazil

Location

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, 04266-010, Brazil

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)

Berlin, 13353, Germany

Location

Charité - Universitaetsmedizin

Berlin, 13353, Germany

Location

Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

IKF Pneumologie GmbH & Co KG

Frankfurt am Main, 60596, Germany

Location

Studiengesellschaft BSF UG.

Halle, 06108, Germany

Location

Studiengesellschaft BSF Unternehmergesellschaft

Halle, 06108, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20359, Germany

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez" de la Universidad Autonoma de Nuevo Leon

Monterrey, N.L., 64460, Mexico

Location

Centro Médico Zambrano Hellion

San Pedro Garza García, Nuevo León, 66278, Mexico

Location

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 SE
• Organization: BioNTech clinical trials patient information

patients@biontech.de

+49 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: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 21, 2021
• Study Start: October 15, 2021
• Primary Completion: July 23, 2023
• Study Completion: July 23, 2023
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); ME (2); US (15); BR (5)