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

Phase 2

Completed

• Conditions: COVID-19; SARS-CoV-2 Infection

• Registration Number: NCT05472038
• Lead Sponsor: BioNTech SE

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-15
• Study First Submitted QC: 2022-07-22
• Study First Posted: 2022-07-25
• Study Start: 2022-07-26
• Primary Completion: 2024-03-26
• Study Completion: 2024-03-26
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-10
• Last Update Posted: 2024-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1454

Inclusion Criteria

1. 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.

2. Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations.

3. Healthy participants (stable pre-existing disease permitted).

4. Capable of giving signed informed consent.

5. 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

1. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines.

2. Known or suspected immunodeficiency.

3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

4. Women who are pregnant or breastfeeding.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Cohort 4 only: History of myocarditis or pericarditis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
All Cohorts: Percentage of participants reporting serious adverse events	For 6 months following the study vaccination	As elicited by the investigational staff
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	At 1 month after study vaccination.	As measured at the central laboratory.
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).	At 1 month after study vaccination.	As measured at the central laboratory.
All Cohorts: Percentage of participants reporting local reactions	For 7 days following the study vaccination	Pain at the injection site, redness, and swelling, as self-reported in electronic diaries
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.	At 1 month after study vaccination.	As measured at the central laboratory.
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..	From before study vaccination (Day 1) to 1 month after study vaccination.	As measured at the central laboratory.
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.	At 1 month after study vaccination	As measured at the central laboratory.
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).	At 1 month after study vaccination.	As measured at the central laboratory.
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.	At 1 month after study vaccination.	As measured at the central laboratory.
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	From before study vaccination (Day 1) to 1 month after study vaccination.	As measured at the central laboratory
All Cohorts: Percentage of participants reporting systemic events	For 7 days following the study vaccination	Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries
All Cohorts: Percentage of participants reporting adverse events	For 1 month following the study vaccination	As elicited by the investigational staff
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.	From before study vaccination (Day 1) to 1 month after study vaccination.	As measured at the central laboratory.
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	At 1 month after study vaccination.	As measured at the central laboratory.
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.	At 1 month after study vaccination.	As measured at the central laboratory.
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	At 1 month after study vaccination	As measured at the central laboratory
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	At 1 month after study vaccination	As measured at the central laboratory

Secondary Outcome Measures

Name	Time	Method
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).	At 1 month after study vaccination.	As measured at the central laboratory.
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).	From before study vaccination (Day 1) to 1 month after study vaccination.	As measured at the central laboratory.
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).	At 1 month after study vaccination.	As measured at the central laboratory.
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.	At 1 month after study vaccination.	As measured at the central laboratory.

Trial Locations

Locations (31)

Anaheim Clinical Trials, LLC; 🇺🇸 Anaheim, California, United States

California Research Foundation; 🇺🇸 San Diego, California, United States

Bayview Research Group, LLC; 🇺🇸 Valley Village, California, United States

Diablo Clinical Research, Inc.; 🇺🇸 Walnut Creek, California, United States

Clinical Research Consulting; 🇺🇸 Milford, Connecticut, United States

Research Centers of America ( Hollywood ); 🇺🇸 Hollywood, Florida, United States

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare; 🇺🇸 Memphis, Tennessee, United States

Acevedo Clinical Research Associates; 🇺🇸 Miami, Florida, United States

Clinical Research Atlanta; 🇺🇸 Stockbridge, Georgia, United States

East-West Medical Research Institute; 🇺🇸 Honolulu, Hawaii, United States

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