Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants

NCT05004181 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: BNT162-172021-003458-22
• Study Type: interventional
• Target: 1,380
• Locations: 4 countries
• Sites: 35

Brief Summary

This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who had received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It also evaluated the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine-experienced participants.

Conditions

SARS-CoV-2 Infection; COVID-19; SARS-CoV-2 Acute Respiratory Disease; SARS (Disease)

Outcome Measures

Primary Outcomes (18)

• All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)

  Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

  from Day 1 to Day 7 after each IMP dose

• All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

  Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

  from Day 1 to Day 7 after each IMP dose

• All Parts - Percentage of Participants Reporting Adverse Events (AEs)

  An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.

  Dose 1 up to 1 month after each dose (all parts)

• All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

  An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.

  Dose 1 up to 6 months after the last dose

• Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

  GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

  GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

  GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 24.

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

  Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

  Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

  Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 25.

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

  Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Cohort B6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.

  1 month

• Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

  Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.

  1 month

• Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

  Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.

  1 month

• Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

  Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.

  1 month

• Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection

  GMR of reference strain NT 3 weeks (3W) after one dose (PD1) of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001 (NCT04368728). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and corresponding CIs (based on the Student t distribution). Assay results below LLOQ were set to 0.5 × LLOQ. GMTs of NTs are presented in the descriptive data section of this outcome measure. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. GMR data are presented in the statistical analysis section.

  3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)

  The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection from the Phase III trial C4591001 (NCT04368728). SR was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a SR. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI was based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.

  3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.

  GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age and number of prior doses. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.529.1 at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 32.

  1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)

• Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.

  SR was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (\<LLOQ), SR was defined as a post-vaccination titer of ≥4× LLOQ. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI were based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.

  1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)

Secondary Outcomes (14)

• Part A - Geometric Mean Titer (GMT) at Each Timepoint

  Day 1 up to Day 421

• Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination

  Day 1 to Day 421

• Part A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point

  Day 1 to Day 421

• Part B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control

  1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

• Part B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control

  1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial

Study Arms (12)

Part A - Cohort 1: 18 to 55 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)

Part A - Cohort 2: 18 to 55 years of age

EXPERIMENTAL

Participants received 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)

Part A - Cohort 3: 18 to 55 years of age

EXPERIMENTAL

Participants received1 dose of BNT162b2 (B.1.1.7) of 30 µg.

Biological: Monovalent BNT162b2 (B.1.1.7)

Part A - Cohort 4: 18 to 55 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.

Biological: Monovalent BNT162b2 (B.1.617.2)

Part A - Cohort 5: 18 to 55 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 of 30 µg.

Biological: BNT162b2

Part A - Cohort 6: 18 to 55 years of age

EXPERIMENTAL

Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)

Part B - Cohort 1: 18 to 85 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)

Part B - Cohort 4: 18 to 85 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.

Biological: Monovalent BNT162b2 (B.1.617.2)

Part B - Cohort 6: 18 to 85 years of age

EXPERIMENTAL

Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)

Part C - Cohort 7: 18 to 85 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 (B.1.1.529.1) of 30 µg.

Biological: Monovalent BNT162b2 (B.1.1.529.1)

Part C - Cohort 8: 18 to 85 years of age

EXPERIMENTAL

Participants received 1 dose of BNT162b2 of 30 µg.

Biological: BNT162b2

Part C - Cohort 9: 18 to 85 years of age

OTHER

Participants received no vaccination within 3 months after Visit 1.

Other: Observational

Interventions

BNT162b2 BIOLOGICAL

Intramuscular (IM)

Part A - Cohort 5: 18 to 55 years of age; Part C - Cohort 8: 18 to 85 years of age

Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) BIOLOGICAL

Intramuscular (IM)

Part A - Cohort 1: 18 to 55 years of age; Part A - Cohort 2: 18 to 55 years of age; Part A - Cohort 6: 18 to 55 years of age; Part B - Cohort 1: 18 to 85 years of age; Part B - Cohort 6: 18 to 85 years of age

Monovalent BNT162b2 (B.1.1.7) BIOLOGICAL

Intramuscular (IM)

Part A - Cohort 3: 18 to 55 years of age

Monovalent BNT162b2 (B.1.617.2) BIOLOGICAL

Intramuscular (IM)

Part A - Cohort 4: 18 to 55 years of age; Part B - Cohort 4: 18 to 85 years of age

Monovalent BNT162b2 (B.1.1.529.1) BIOLOGICAL

Intramuscular (IM)

Part C - Cohort 7: 18 to 85 years of age

Observational OTHER

No vaccination within 3 months after Visit 1.

Part C - Cohort 9: 18 to 85 years of age

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
• Volunteers who at the time of consent were:
• Part A: 18 to 55 years old.
• Part B and Part C: 18 to 85 years old (\~60% should be 18 to 55 years old and \~40% 56 to 85 years old).
• For Cohorts 1 to 5: In Part A, who had received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
• For Cohort 6: Were COVID-19 vaccine-naïve and had not experienced COVID-19 based on their medical history.
• Were willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
• Were overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).
• Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, could be included.
• Note: Volunteers who had hepatitis C (HCV) infection, but had completed curative treatment based on the medical history could be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history could not be included.
• Agreed not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
• Women of childbearing potential (WOCBP) had to test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
• WOCBP had to agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
• WOCBP had to confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
• WOCBP had to agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.

You may not qualify if:

• Any existing condition which could have affected vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
• Any bleeding diathesis or condition associated with prolonged bleeding that could have, in the opinion of the investigator, contraindicated intramuscular injection.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, made the participant inappropriate for the trial.
• Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
• Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease was not considered relevant for participation in this trial in the investigator's judgment.
• History of COVID-19 and/or 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) evidence of prior infection with SARS CoV 2 at screening (Visit 0).
• Note: not applicable for Part C.
• History of Guillain-Barré syndrome.
• Known or suspected immunodeficiency.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
• History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
• Had received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).
• Note: not applicable for Part C.
• Had received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
• Had received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard of care vaccinations should been planned with the trial IMP administrations in mind.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (35)

Collaborative Neuroscience Network LLC

Long Beach, California, 90806, United States

Location

California Research Foundation

San Diego, California, 92123, United States

Location

Clinical Research Consulting, Llc

Milford, Connecticut, 06460, United States

Location

Stamford Therapeutics Consortium

Stamford, Connecticut, 06905, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Meridian Clinical Research

Savannah, Georgia, 31406, United States

Location

Medpharmics, LLC

Gulfport, Mississippi, 39503, United States

Location

Amici Clinical Research

Warren Township, New Jersey, 07059, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43213, United States

Location

ARC Clinical Research

Austin, Texas, 78745, United States

Location

North Texas Infectious Diseases Consultants

Dallas, Texas, 75246, 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

CRS Clinical Research Services Berlin

Berlin, 13353, Germany

Location

IKF Institut fuer klinische Forschung Frankfurt

Frankfurt am Main, 60596, Germany

Location

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Location

Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher

Stuhr, 28816, Germany

Location

JOSHA Research

Bloemfontein, Free State, 09301, South Africa

Location

Langeberg Medicross Medical Centre

Kraaifontein, Western Cape, 75070, South Africa

Location

Paarl Research Centre

Paarl, Western Cape, 07646, South Africa

Location

Synexus Helderberg Clinical Trial Centre

Somerset West, Western Cape, 07130, South Africa

Location

Worthwhile Clinical Trials

Benoni, 01501, South Africa

Location

Tiervlei Trial Centre

Cape Town, 07530, South Africa

Location

Midrand Medical Centre

Halfway House, 01685, South Africa

Location

Newtown Clinical Research

Johannesburg, 02113, South Africa

Location

Global Clinical Trials

Pretoria, 00001, South Africa

Location

Botho ke Bontle Health Service

Pretoria, 00122, South Africa

Location

Synexus SA Stanza Clinical Research Centre

Pretoria, 00122, South Africa

Location

Jongaie Research, Medicross Pretoria West

Pretoria, 00183, South Africa

Location

Ankara University Faculty of Medicine, Avicenna Hospital

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe University Hospital

Ankara, 06100, Turkey (Türkiye)

Location

Bagcilar Medipol Mega University Hospital

Istanbul, 34214, Turkey (Türkiye)

Location

Istanbul University Medical Faculty

Istanbul, 34390, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Related Publications (3)

• Muik A, Quandt J, Lui BG, Bacher M, Lutz S, Grunenthal M, Toker A, Grosser J, Ozhelvaci O, Blokhina O, Shpyro S, Vogler I, Salisch N, Tureci O, Sahin U. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1. Cell Rep. 2024 Aug 27;43(8):114567. doi: 10.1016/j.celrep.2024.114567. Epub 2024 Aug 3.

  PMID: 39097927 DERIVED

• Muik A, Lui BG, Quandt J, Diao H, Fu Y, Bacher M, Gordon J, Toker A, Grosser J, Ozhelvaci O, Grikscheit K, Hoehl S, Kohmer N, Lustig Y, Regev-Yochay G, Ciesek S, Beguir K, Poran A, Vogler I, Tureci O, Sahin U. Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T cell immunity. Cell Rep. 2023 Aug 29;42(8):112888. doi: 10.1016/j.celrep.2023.112888. Epub 2023 Jul 31.

  PMID: 37527039 DERIVED

• Muik A, Lui BG, Bacher M, Wallisch AK, Toker A, Couto CIC, Guler A, Mampilli V, Schmitt GJ, Mottl J, Ziegenhals T, Fesser S, Reinholz J, Wernig F, Schraut KG, Hefesha H, Cai H, Yang Q, Walzer KC, Grosser J, Strauss S, Finlayson A, Kruger K, Ozhelvaci O, Grikscheit K, Kohmer N, Ciesek S, Swanson KA, Vogel AB, Tureci O, Sahin U. Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice. Sci Immunol. 2022 Dec 23;7(78):eade9888. doi: 10.1126/sciimmunol.ade9888. Epub 2022 Dec 23.

  PMID: 36378074 DERIVED

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome; Disease

Interventions

BNT162 Vaccine; Watchful Waiting

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Results Point of Contact

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

patients@biontech.de

+49 6131 9084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 13, 2021
• Study Start: August 25, 2021
• Primary Completion: August 16, 2023
• Study Completion: October 4, 2023
• Last Updated: November 22, 2024
• Results First Posted: November 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (12); DE (4); US (14); TU (5)