A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Variants in Healthy Individuals

Study Overview
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Brief Summary
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The purpose of this clinical protocol is to learn about the safety, tolerability, and immunogenicity of new BNT162b2 RNA-based vaccine candidates targeting new variants of SARS-CoV-2 in healthy people. Substudy A: This study will evaluate the safety, tolerability, and immunogenicity of BNT162b2 (Omi XBB.1.5) given as a single 30 µg dose, in people who are 12 years of age and older, who previously received at least 3 doses of a US-authorized mRNA COVID-19 vaccine, with the most recent dose being an Omicron BA.4/BA.5-adapted bivalent vaccine received at least 150 days before the study vaccination (Visit 1). The study is about 6 months long for each participant. Participants will have at least 5 visits to the clinic. At each clinic visit a blood sample will be taken. At least 1 nasal swab will taken. Substudy B: This study will evaluate the safety, tolerability, and immunogenicity of BNT162b2 (Omi XBB.1.5) given as a single 30 µg dose, in people who are 12 years of age and older, who are COVID-19 vaccine-naïve who have had any positive SARS-CoV-2 test result >28 days before study vaccine administration. The study is about 6 months long for each participant. Participants will have at least 5 visits to the clinic. At each clinic visit a blood sample will be taken. At least 1 nasal swab will taken.

Official Title
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A PHASE 2/3 PROTOCOL TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b2 RNA-BASED VACCINE CANDIDATES FOR SARS-CoV-2 NEW VARIANTS IN HEALTHY INDIVIDUALS

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Biological: BNT162b2 (Omi XBB.1.5)


Participation Criteria
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Eligibility Criteria
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SSA Inclusion Criteria: Received at least 3 prior doses of a US-authorized mRNA COVID-19 vaccine, with the most recent dose being a US-authorized Omicron BA.4/BA.5-adapted bivalent vaccine received at least 150 days before Visit 1 (Day 1). 12 years of age and older Healthy participants (stable pre-existing disease permitted). Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations. Capable of giving, or parent(s)/legal guardian capable of giving, signed informed consent. 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. Immunocompromised with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 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. Any 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. History of myocarditis or pericarditis. Receipt of 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. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, used for the treatment or prevention of COVID-19 or those that are considered immunosuppressive, from 60 days before study vaccination or planned receipt throughout the study. Participation in other studies involving receipt of other study intervention within 28 days before enrollment. Anticipated participation in other studies involving other study intervention from enrollment 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. SSB Inclusion Criteria: COVID-19 vaccine-naïve. Any positive SARS-CoV-2 test result >28 days before study intervention administration. 12 years of age and older. Healthy participants (stable pre-existing disease permitted). Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations. Capable of giving or parent(s)/legal guardian capable of giving, signed informed consent. 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. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 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. Any 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 myocarditis or pericarditis. Receipt of 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. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for the treatment or prevention of COVID-19 or those that are considered immunosuppressive, from 60 days before study intervention administration or planned receipt throughout the study. Participation in other studies involving receipt of other study intervention within 28 days before enrollment. Anticipated participation in other studies involving other study intervention from enrollment 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.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 2/3, controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSA: Group 1<br>Participants 12 years of age and older, COVID-19 vaccine-experienced will receive 30 µg of BNT162b2 (Omi XBB.1.5) at Visit 1. | Biological: BNT162b2 (Omi XBB.1.5)<br>* BNT162b2 monovalent (Omicron XBB.1.5)<br>|
| Experimental: SSB: Group 2<br>Participants 12 years of age and older who were previously exposed to SARS-CoV-2 and are COVID-19 vaccine-naïve will receive 30 μg of BNT162b2 (Omi XBB.1.5) at Visit 1 | Biological: BNT162b2 (Omi XBB.1.5)<br>* BNT162b2 monovalent (Omicron XBB.1.5)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SSA: Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling, as self-reported in electronic diaries. | For up to 7 days following the study vaccination | 
| SSA: 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 up to 7 days following the study vaccination | 
| SSA: Percentage of participants reporting adverse events | As elicited by the investigational staff | Through 1 month after the study vaccination | 
| SSA: Percentage of participants reporting serious adverse events | As elicited by the investigational staff | Through 6 months after the study vaccination | 
| SSA: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron XBB.1.5- and Omicron BA.4/BA.5-neutralizing antibody levels for BNT162b2 (Omi XBB.1.5) 30 µg | As measured at the central laboratory | At 1 month after the study vaccination | 
| SSA: Geometric Mean Fold Rise (GMFR; change between 2 timepoints) of SARS-CoV-2 Omicron XBB.1.5-and Omicron BA.4/BA.5-neutralizing antibody levels for BNT162b2 (Omi XBB.1.5) 30 µg | As measured at the central laboratory | From before study vaccination (Day 1) to 1 month after study vaccination | 
| SSA: Percentages of participants with seroresponse to BNT162b2 (Omi XBB.1.5) 30 µg in terms of GMTs of SARS-CoV-2 Omicron XBB.1.5- and Omicron BA.4/BA.5-neutralizing antibody levels | As measured at the central laboratory | At 1 month after the study vaccination | 
| SSB: Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling, as self-reported in electronic diaries. | For up to 7 days following the study vaccination | 
| SSB: 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 up to 7 days following the study vaccination | 
| SSB: Percentage of participants reporting adverse events | As elicited by the investigational staff. | Through 1 month after the study vaccination | 
| SSB: Percentage of participants reporting serious adverse events | As elicited by the investigational staff. | Through 6 months after the study vaccination | 
| SSB: Geometric Mean Ratio (GMR) of the SARS-CoV-2 XBB.1.5-neutralizing titers after BNT162b2 (Omi XBB.1.5) 30 μg given as single dose to COVID-19 vaccine-naïve subjects to BNT162b2 (Omi XBB.1.5) 30 μg given to vaccine-experienced participants in SSA. | As measured at the central laboratory | At 1 month after vaccination. | 
| Difference in percentages of subjects with seroresponse to XBB.1.5 strain after BNT162b2 (Omi XBB.1.5) 30 μg given as single dose to COVID-19 vaccine-naïve subjects compared to BNT162b2 (Omi XBB.1.5) 30 μg given to vaccine experienced subjects in SSA | As measured at the central laboratory | At 1 month after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus, COVID-19, SARS-CoV-2, RNA Vaccine, Vaccine-naïve, Vaccine