Clinical trial NCT05472038: A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2 Infection
COVID-19
Keywords: SARS-CoV-2 infection
COVID-19
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2022-07-25
Enrollment: 1454
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1/2/3, randomized, active-controlled, parallel group study.
Primary purpose: PREVENTION

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).


Eligibility criteria: 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

Primary outcomes:
measure: All Cohorts: Percentage of participants reporting local reactions
timeFrame: For 7 days following the study vaccination
measure: All Cohorts: Percentage of participants reporting systemic events
timeFrame: For 7 days following the study vaccination
measure: All Cohorts: Percentage of participants reporting adverse events
timeFrame: For 1 month following the study vaccination
measure: All Cohorts: Percentage of participants reporting serious adverse events
timeFrame: For 6 months following the study vaccination
measure: 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
timeFrame: Before study vaccination (Day 1).
measure: 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
timeFrame: At 1 month after study vaccination.
measure: 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.
timeFrame: From before study vaccination (Day 1) to 1 month after study vaccination.
measure: 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.
timeFrame: At 1 month after study vaccination.
measure: 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
timeFrame: Before study vaccination (Day 1).
measure: 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
timeFrame: At 1 month after study vaccination.
measure: 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..
timeFrame: From before study vaccination (Day 1) to 1 month after study vaccination.
measure: 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.
timeFrame: At 1 month after study vaccination
measure: 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).
timeFrame: At 1 month after study vaccination.
measure: 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).
timeFrame: At 1 month after study vaccination.
measure: 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.
timeFrame: At 1 month after study vaccination.
measure: 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.
timeFrame: At 1 month after study vaccination.
measure: 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
timeFrame: Before study vaccination (Day 1)
measure: 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
timeFrame: At 1 month after study vaccination
measure: 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
timeFrame: From before study vaccination (Day 1) to 1 month after study vaccination.
measure: 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
timeFrame: At 1 month after study vaccination
Secondary outcomes:
measure: 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).
timeFrame: At 1 month after study vaccination.
measure: 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).
timeFrame: Before study vaccination (Day 1).
measure: 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).
timeFrame: At 1 month after study vaccination.
measure: 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).
timeFrame: From before study vaccination (Day 1) to 1 month after study vaccination.
measure: 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.
timeFrame: At 1 month after study vaccination.
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Milford
country: United States
facility: Clinical Research Consulting
state: Connecticut
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Bardstown
country: United States
facility: Kentucky Pediatric/ Adult Research
state: Kentucky
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha
state: Nebraska
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Charlotte
country: United States
facility: Accellacare - Charlotte
state: North Carolina
city: Charlotte
country: United States
facility: Accellacare - Charlotte
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest Life Sciences, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare - Wilmington
state: North Carolina
city: Cleveland
country: United States
facility: Senders Pediatrics
state: Ohio
city: Columbus
country: United States
facility: Centricity Research Columbus Ohio Multispecialty
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Northwest Center for Health Research
state: Oregon
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Austin
country: United States
facility: Tekton Research, LLC.
state: Texas
city: Houston
country: United States
facility: DM Clinical Research - Bellaire
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research San Antonio
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic South
state: Utah
city: Midlothian
country: United States
facility: Virginia Research Center
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: