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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05472038
• Other study ID #: C4591044
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 26, 2022
• Est. completion date: March 26, 2024

Study information

• Verified date: April 2024
• Source: BioNTech SE
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1454
• Est. completion date: March 26, 2024
• Est. primary completion date: March 26, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Biological:
• BNT162b5 Bivalent (WT/OMI BA.2)
BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.2]
• BNT162b2 Bivalent (WT/OMI BA.1)
BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.1]
• BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
• BNT162b5 Bivalent (Original/OMI BA.4/BA.5)
BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
• BNT162b6 Bivalent (Original/OMI BA.4/BA.5)
BNT162b6 Wild Type and BNT162b6 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
• BNT162b7 Bivalent (Original/OMI BA.4/BA.5)
BNT162b7 Wild Type and BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
• BNT162b7 Monovalent (OMI BA.4/BA.5)
BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Benchmark Research	Austin	Texas
United States	Tekton Research, LLC.	Austin	Texas
United States	Kentucky Pediatric/ Adult Research	Bardstown	Kentucky
United States	Accellacare - Charlotte	Charlotte	North Carolina
United States	Accellacare - Charlotte	Charlotte	North Carolina
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Senders Pediatrics	Cleveland	Ohio
United States	Centricity Research Columbus Ohio Multispecialty	Columbus	Ohio
United States	PharmQuest Life Sciences, LLC	Greensboro	North Carolina
United States	Research Centers of America ( Hollywood )	Hollywood	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	DM Clinical Research - Bellaire	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Jacksonville	Florida
United States	Clinical Neuroscience Solutions Inc.	Memphis	Tennessee
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Memphis	Tennessee
United States	Acevedo Clinical Research Associates	Miami	Florida
United States	Virginia Research Center	Midlothian	Virginia
United States	Clinical Research Consulting	Milford	Connecticut
United States	Velocity Clinical Research, Omaha	Omaha	Nebraska
United States	Kaiser Permanente Northwest Center for Health Research	Portland	Oregon
United States	Rochester Clinical Research, LLC	Rochester	New York
United States	Sundance Clinical Research	Saint Louis	Missouri
United States	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah
United States	IMA Clinical Research San Antonio	San Antonio	Texas
United States	California Research Foundation	San Diego	California
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	DM Clinical Research	Tomball	Texas
United States	Bayview Research Group, LLC	Valley Village	California
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Accellacare - Wilmington	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	All Cohorts: Percentage of participants reporting adverse events	As elicited by the investigational staff	For 1 month following the study vaccination
Primary	All Cohorts: Percentage of participants reporting serious adverse events	As elicited by the investigational staff	For 6 months following the study vaccination
Primary	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).
Primary	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.
Primary	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.
Primary	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.
Primary	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).
Primary	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.
Primary	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.
Primary	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
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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)
Primary	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
Primary	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.
Primary	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	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.
Secondary	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).
Secondary	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.
Secondary	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.
Secondary	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.

External Links

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