A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals

Study Overview
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Brief Summary
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The purpose of this clinical trial is to learn about the safety, tolerability and immunogenicity of BNT162b RNA-based SARS-CoV-2 vaccine candidates in adults to prevent COVID-19. For all cohorts (groups of participants), this study is seeking participants who are healthy (who may have preexisting disease if it is stable); All participants will receive a single dose of the study vaccine at the first study clinic and will return to the study clinic at least 4 more times. At each clinic visit, a blood sample will be taken. The study is about 6 months long for each participant. The vaccine candidates in this study are investigational but are very similar to BNT162b2 (Comirnaty), a COVID-19 RNA vaccine approved for use in the US and in many countries. For Cohort 1, this study included participants who were: 18 through 55 years of age have received 1 booster dose of a US-authorized COVID-19 vaccine, with the last dose being 90 or more days before Visit 1 of this study. All participants in Cohort 1 will receive 1 of the 2 study vaccines at a 30 microgram dose: BNT162b5 Bivalent (WT/OMI BA.2) or BNT162b2 Bivalent (WT/OMI BA.1). For Cohort 2, this study included participants who were: 12 years of age and older have received 3 prior doses of 30 micrograms BNT162b2, with the last dose being 150 to 365 days before Visit 1 of this study. Participants 12 through 17 years of age will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 micrograms. Participants 18 years and older will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at either a 30 microgram or a 60 microgram dose. For Cohort 3, this study included participants who were: 18 years of age and older have received 3 prior doses of 30 micrograms BNT162b2, with the last dose being 150 to 365 days before Visit 1 of this study. Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 micrograms. For Cohort 4, this study is seeking participants who are: 18 through 55 years of age have received 3 or 4 prior doses of a US-authorized mRNA COVID-19 vaccine (and dose level), with the last dose being a US-authorized BA.4/BA.5-adapted bivalent vaccine and dose level at least 150 days before Visit 1 of this study. All participants in Cohort 4 will receive 1 of the 5 study vaccines at a 30 microgram dose: BNT162b2 Bivalent (Original/ OMI BA.4/BA.5), BNT162b5 Bivalent (Original/OMI BA.4/BA.5), BNT162b6 Bivalent (Original/OMI BA.4/BA.5), BNT162b7 Bivalent (Original/OMI BA.4/BA.5) or BNT162b7 Monovalent (OMI BA.4/BA.5).

Official Title
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AN INTERVENTIONAL, RANDOMIZED, ACTIVE-CONTROLLED, PHASE 1/2/3 STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b RNA-BASED VACCINE CANDIDATES IN COVID-19 VACCINE-EXPERIENCED HEALTHY INDIVIDUALS

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Biological: BNT162b5 Bivalent (WT/OMI BA.2)
* Biological: BNT162b2 Bivalent (WT/OMI BA.1)
* Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
* Biological: BNT162b5 Bivalent (Original/OMI BA.4/BA.5)
* Biological: BNT162b6 Bivalent (Original/OMI BA.4/BA.5)
* Biological: BNT162b7 Bivalent (Original/OMI BA.4/BA.5)
* Biological: BNT162b7 Monovalent (OMI BA.4/BA.5)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Cohort 1: 18 through 55 years of age. Cohort 2: 12 years of age and older. Cohort 3: 18 years of age and older. Cohort 4: 18 through 55 years of age. Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations. Healthy participants (stable pre-existing disease permitted). Capable of giving signed informed consent. Prior COVID-19 vaccination history: Cohort 1: - Received of 1 booster dose of a US-authorized COVID-19 vaccine, with the dose being 90 or more days before first study visit. Documented receipt of all prior COVID-19 vaccines is required. Cohorts 2 and 3: - Received 3 prior doses of 30 micrograms BNT162b2, with last dose being 150 to 365 days before first study visit. Documented receipt of all prior COVID-19 vaccines is required. Cohort 4: - Received 3 or 4 prior doses of a US-authorized mRNA COVID-19 vaccine (and dose level), with the last dose being a US-authorized Omicron BA.4/BA.5-adapted vaccine and dose level at least 150 days before first study visit. Documented receipt of all prior COVID-19 vaccines is required. Exclusion Criteria: History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines. Known or suspected immunodeficiency. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Women who are pregnant or breastfeeding. Other medical or psychiatric condition, or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Immunosuppressants/radiotherapy: Cohorts 1 and 2: Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before study vaccination through end of study. Cohorts 3 and 4: Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease), or radiotherapy, within 60 days before enrollment or planned receipt through conclusion of the study. Blood/plasma products, immunoglobulin, or monoclonal antibodies: Cohorts 1, 2, 3: Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study vaccination or planned receipt throughout the study. Cohort 4: Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for treatment/prevention of COVID-19 or those considered immunosuppressive, from 60 days before study vaccination or planned receipt throughout the study. Other study participation: Cohorts 1 and 2: Participation in other studies involving a study intervention within 28 days before randomization. Anticipated participation in other studies within 28 days after receipt of study intervention in this study. Cohorts 3 and 4: Participation in other studies involving receipt of a study intervention within 28 days before randomization. Anticipated participation in other studies involving a study intervention from randomization through the end of this study. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. Cohort 4 only: History of myocarditis or pericarditis

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1/2/3, randomized, active-controlled, parallel group study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: BNT162b5 Bivalent (WT/OMI BA.2)<br>Participants will receive 30 µg of BNT162b5 Bivalent (WT/OMI BA.2) at Visit 1. | Biological: BNT162b5 Bivalent (WT/OMI BA.2)<br>* BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.2]<br>|
| Experimental: Cohort 1: BNT162b2 Bivalent (WT/OMI BA.1)<br>Participants will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.1) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.1]<br>|
| Experimental: Cohort 2 -Group 1: 12-17 years; 30 µg<br>Participants 12-17 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 2 - Group 2: 18-55 years; 30 µg<br>Participants 18-55 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 2 - Group 3: 18-55 years; 60 µg<br>Participants 18-55 years old will receive 60 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 2 - Group 4: >55 years; 30 µg<br>Participants over 55 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 2 - Group 5: >55 years; 60 µg<br>Participants over 55 years old will receive 60 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 3 - Group 1: 18-55 years; 30 µg<br>Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 3 - Group 2: >55 years; 30 µg<br>Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg at Visit 1. | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Active Comparator: Cohort 4: BNT162b2 Bivalent (Original/OMI BA.4/BA.5)<br>Participants will receive 30 µg of BNT162b2 Bivalent (Original/OMI BA.4/BA.5) at Visit 1 | Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)<br>* BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 4: BNT162b5 Bivalent (Original/OMI BA.4/BA.5)<br>Participants will receive 30 µg of BNT162b5 Bivalent (Original/OMI BA.4/BA.5) at Visit 1 | Biological: BNT162b5 Bivalent (Original/OMI BA.4/BA.5)<br>* BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 4: BNT162b6 Bivalent (Original/OMI BA.4/BA.5)<br>Participants will receive 30 µg of BNT162b6 Bivalent (Original/OMI BA.4/BA.5) at Visit 1 | Biological: BNT162b6 Bivalent (Original/OMI BA.4/BA.5)<br>* BNT162b6 Wild Type and BNT162b6 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 4: BNT162b7 Bivalent (Original/OMI BA.4/BA.5)<br>Participants will receive 30 µg of BNT162b7 Bivalent (Original/OMI BA.4/BA.5) at Visit 1 | Biological: BNT162b7 Bivalent (Original/OMI BA.4/BA.5)<br>* BNT162b7 Wild Type and BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|
| Experimental: Cohort 4: BNT162b7 Monovalent (OMI BA.4/BA.5)<br>Participants will receive 30 µg of BNT162b7 Monovalent (OMI BA.4/BA.5) at Visit 1 | Biological: BNT162b7 Monovalent (OMI BA.4/BA.5)<br>* BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cohorts: Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling, as self-reported in electronic diaries | For 7 days following the study vaccination | 
| All Cohorts: Percentage of participants reporting systemic events | Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries | For 7 days following the study vaccination | 
| All Cohorts: Percentage of participants reporting adverse events | As elicited by the investigational staff | For 1 month following the study vaccination | 
| All Cohorts: Percentage of participants reporting serious adverse events | As elicited by the investigational staff | For 6 months following the study vaccination | 
| Cohort 1: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.2), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b5 Bivalent (WT/OMI BA.2) 30 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg | As measured at the central laboratory. | Before study vaccination (Day 1). | 
| Cohort 1: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.2), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b5 Bivalent (WT/OMI BA.2) 30 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohort 1: Geometric Mean Fold Rise (GMFR; change between 2 timepoints) of SARS-CoV-2 Omicron (BA.2), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b5 Bivalent (WT/OMI BA.2) 30 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg. | As measured at the central laboratory. | From before study vaccination (Day 1) to 1 month after study vaccination. | 
| Cohort 1: Percentages of participants with seroresponse to BNT162b5 Bivalent (WT/OMI BA.2) 30 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg in terms of GMTs of SARS-CoV-2 Omicron (BA.2), Omicron (BA.1), and reference strain neutralizing antibody levels. | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohort 2: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.4/BA.5), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg or 60 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg or 60 µg | As measured at the central laboratory. | Before study vaccination (Day 1). | 
| Cohort 2: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.4/BA.5), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg or 60 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg or 60 µg | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohort 2: GMFR (change between 2 timepoints) of SARS-CoV-2 Omicron (BA.4/BA.5), Omicron (BA.1), and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg or 60 µg and BNT162b2 Bivalent (WT/OMI BA.1) 30 µg or 60 µg.. | As measured at the central laboratory. | From before study vaccination (Day 1) to 1 month after study vaccination. | 
| Cohort 2: % of participants with seroresponse to BNT162b2 Bivalent(WT/OMI BA.4/BA.5) 30µg or 60µg and BNT162b2 Bivalent(WT/OMI BA.1) 30µg or 60µg for GMTs of SARS-CoV-2 Omicron(BA.4/BA.5), Omicron(BA.1), and reference strain neutralizing antibody levels. | As measured at the central laboratory. | At 1 month after study vaccination | 
| Cohorts 2+3 (>55 yrs) Superiority analysis: Geometric Mean Ratio (GMR) of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg to BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohorts 2+3 (>55 yrs) Noninferiority analysis: Differences in %s of participants with seroresponse to SARS-CoV-2 Omicron BA.4/BA.5 after vaccination with BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg or BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohorts 2+3 (18-55 yrs), C2+3 (>55 yrs) Noninferiority analysis: GMR of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg in participants 18-55 yrs compared to participants >55 yrs. | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohorts 2+3 (18-55 yrs), C2+3 (>55 yrs) Noninferiority analysis: Differences in %s of pts with seroresponse to SARS-CoV-2 Omicron BA.4/BA.5 after vaccination with BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg in pts 18-55 yrs compared to pts >55 yrs. | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohort 4: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for 30µg BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 Bivalent and BNT162b7 Monovalent | As measured at the central laboratory | Before study vaccination (Day 1) | 
| Cohort 4: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for 30µg BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 Bivalent and BNT162b7 Monovalent | As measured at the central laboratory | At 1 month after study vaccination | 
| Cohort 4: GMFR (change between 2 timepoints) of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for 30µg BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 Bivalent and BNT162b7 Monovalent | As measured at the central laboratory | From before study vaccination (Day 1) to 1 month after study vaccination. | 
| Cohort 4: % of participants with seroresponse to 30µg BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 Bivalent and BNT162b7 Monovalent for GMTs of SARS-CoV-2 Omicron(BA.4/BA.5), and reference strain neutralizing antibody levels | As measured at the central laboratory | At 1 month after study vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 2+3 (>55 yrs) Noninferiority analysis: GMR of SARS-CoV-2 reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg to BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohorts 2+3 (18-55 yrs), Cohorts 2+3 (>55 yrs): GMTs of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg and BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | Before study vaccination (Day 1). | 
| Cohorts 2+3 (18-55 yrs), Cohorts 2+3 (>55 yrs): GMTs of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg and BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | At 1 month after study vaccination. | 
| Cohorts 2+3 (18-55 yrs), C2+3 (>55 yrs): GMFR (change between 2 timepoints) of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels for BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg and BNT162b2 30 μg (C4591031 Substudy E). | As measured at the central laboratory. | From before study vaccination (Day 1) to 1 month after study vaccination. | 
| Cohorts 2+3 (18-55 yrs), C2+3 (>55 yrs): % of participants with seroresponse to BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 μg and BNT162b2 30 μg (C4591031 SSE) for GMTs of SARS-CoV-2 Omicron (BA.4/BA.5) and reference strain neutralizing antibody levels. | As measured at the central laboratory. | At 1 month after study vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 infection, COVID-19