A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of Multiple Production Lots and Dose Levels of BNT162b2 RNA-Based COVID-19 Vaccines Against COVID-19 in Healthy Participants

• ClinicalTrials.gov Identifier: NCT04713553
• Recruitment Status: Completed
• First Posted: January 19, 2021
• Last Update Posted: February 23, 2022
• Sponsor: BioNTech SE
• Collaborator: Pfizer
• Information provided by (Responsible Party): BioNTech SE

Study Description

Brief Summary:

This is a Phase 3, randomized, observer-blind study in healthy individuals.

The primary study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate (BNT162b2):

• As a 30-microgram dose, administered from 1 of 4 manufacturing lots (batches)
• As a 20-microgram dose, administered from 1 of the manufacturing lots
• As a 2-dose (separated by 21 days) schedule
• In people 12 through 50 years of age

The booster study will evaluate the safety, tolerability, and immunogenicity of 2 SARS-CoV-2 RNA vaccine candidates (BNT162b2 and BNT162b2.B.1.351):

• Each as a 30-microgram dose
• Each as a 1-dose booster vaccine, administered approximately 3 months after Dose 2
• In people 18 through 50 years of age

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2 Infection; COVID-19	Biological: BNT162b2; Biological: BNT162b2.B.1.351	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1530 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE PRODUCTION LOTS AND DOSE LEVELS OF THE VACCINE CANDIDATE BNT162b2 AGAINST COVID-19 IN HEALTHY PARTICIPANTS 12 THROUGH 50 YEARS OF AGE AND THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b2 RNA-BASED COVID-19 VACCINE CANDIDATES AS A BOOSTER DOSE IN HEALTHY PARTICIPANTS 18 THROUGH 50 YEARS OF AGE
• Actual Study Start Date: February 15, 2021
• Actual Primary Completion Date: July 22, 2021
• Actual Study Completion Date: July 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1; 30-microgram dose of US manufactured drug substance (Lot 1)	Biological: BNT162b2; Intramuscular injection
Experimental: Arm 2; 30-microgram dose of US manufactured drug substance (Lot 2)	Biological: BNT162b2; Intramuscular injection
Experimental: Arm 3; 30-microgram dose of US manufactured drug substance (Lot 3)	Biological: BNT162b2; Intramuscular injection
Experimental: Arm 4; 30-microgram dose of EU manufactured drug substance (Lot 4)	Biological: BNT162b2; Intramuscular injection
Experimental: Arm 5; 20-microgram dose of US manufactured drug substance (corresponding to Arm 1, 2 or 3 lot)	Biological: BNT162b2; Intramuscular injection
Experimental: Booster 1: BNT162b2; 30-microgram dose	Biological: BNT162b2; Intramuscular injection
Experimental: Booster 2: BNT162b2.B.1.351; 30-microgram dose	Biological: BNT162b2.B.1.351; Intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Geometric Mean Ratio (GMR) of SARS-CoV-2 full-length S-binding antibody levels between US lots (Arms 1, 2 and 3) in participants without evidence of infection during the study [ Time Frame: At 1 month after Dose 2 ]
   As measured at the central laboratory
2. GMR of SARS-CoV-2 full-length S-binding antibody levels between the EU lot (Arm 4) and pooled US lots (Arms 1, 2, and 3) in participants without evidence of infection during the study [ Time Frame: At 1 month after Dose 2 ]
   As measured at the central laboratory
3. GMR of SARS-CoV-2 neutralizing antibody levels between the 20-microgram dose group (Arm 5) and the corresponding 30-microgram dose group (Arm 1, 2, or 3) in participants without evidence of SARS-C0V-2 infection during the study. [ Time Frame: At 1 month after Dose 2 ]
   As measured at the central laboratory
4. Percentage of participants reporting local reactions [ Time Frame: For 7 days after Dose 1 and Dose 2. For 7 days after Dose 3 (booster). ]
   Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.
5. Percentage of participants reporting systemic events [ Time Frame: For 7 days after Dose 1 and Dose 2. For 7 days after Dose 3 (booster). ]
   Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries.
6. Percentage of participants reporting adverse events [ Time Frame: From Dose 1 through 1 month after Dose 2. From Dose 3 to 1 month after Dose 3. ]
   As elicited by investigational site staff
7. Percentage of participants reporting serious adverse events [ Time Frame: From Dose 1 through 1 month after Dose 2. From Dose 3 to 1 month after Dose 3. ]
   As elicited by investigational site staff
8. Geometric Mean Titers (GMT) of SARS-CoV-2 reference strain and B.1.351 strain neutralizing antibody levels for Booster Arm 1 (BNT162b2) and Booster Arm 2 (BNT162b2.B.1.351). [ Time Frame: Before Dose 1, 1 month after Dose 2, before Dose 3, and 1 week after and 1 month after Dose 3. ]
   As measured at the central laboratory
9. Geometric Mean IgG Concentrations (GMC) of SARS-CoV-2 full-length S-binding antibody levels for Booster Arm 1 (BNT162b2) and Booster Arm 2 (BNT162b2.B.1.351). [ Time Frame: Before Dose 1, 1 month after Dose 2, before Dose 3, and 1 week after and 1 month after Dose 3. ]
   As measured at the central laboratory
10. Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 reference strain and B.1.351 strain neutralizing antibody levels for Booster Arm 1 (BNT162b2) and Booster Arm 2 (BNT162b2.B.1.351). [ Time Frame: From 1 month after Dose 2 to 1 week after and 1 month after Dose 3 and from before Dose 3 to 1 week after and 1 month after Dose 3. ]
    As measured at the central laboratory
11. Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 full-length S-binding antibody levels for Booster Arm 1 (BNT162b2) and Booster Arm 2 (BNT162b2.B.1.351). [ Time Frame: From 1 month after Dose 2 to 1 week after and 1 month after Dose 3 and from before Dose 3 to 1 week after and 1 month after Dose 3. ]
    As measured at the central laboratory
12. Percentages of participants with seroresponse (based on neutralizing titers) to the reference strain. [ Time Frame: At 1 month after Sode 2, before Dose 3, and 1 week after and 1 month after Dose 3. ]
    As measured at the central laboratory
13. Percentages of participants with seroresponse (based on neutralizing titers) to the B.1.351 strain. [ Time Frame: At 1 month after Sode 2, before Dose 3, and 1 week after and 1 month after Dose 3. ]
    As measured at the central laboratory

Secondary Outcome Measures :

1. Geometric Mean Concentrations (GMCs) of SARS-CoV-2 full-length S-binding antibody levels in participants vaccinated with one of the 30-microgram lots (US or EU). [ Time Frame: At baseline (before Dose 1) and at 1 month after Dose 2 ]
   As measured at the central laboratory
2. Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 full-length S-binding antibody levels in participants vaccinated with one of the 30-microgram lots (US or EU) [ Time Frame: From baseline (before Dose 1) to 1 month after Dose 2 ]
   As measured at the central laboratory
3. GMTs of SARS CoV-2 neutralizing antibody levels in participants vaccinated with the 20-microgram or 30-microgram dose (from same US lot) [ Time Frame: At baseline (before Dose 1) and 1 month after Dose 2 ]
   As measured at the central laboratory
4. GMFRs of SARS-CoV-2 neutralizing antibody levels in participants vaccinated with the 20-microgram or 30-microgram dose (from same US lot). [ Time Frame: From baseline (before Dose 1) to 1 month after Dose 2 ]
   As measured at the central laboratory

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Primary study: Male or female participants between the ages of 12 and 50 years, inclusive, at randomization.
• Booster study: Male or female participants between the ages of 18 and 50 years, inclusive, at rerandomization.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
• Capable of giving personal signed informed consent/have parent(s)/legal guardian capable of giving signed informed consent.

Exclusion Criteria:

• Other 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.
• Known infection with HIV, HCV, or HBV.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.

• Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID 19.

  . 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.
• Primary study: Previous vaccination with any coronavirus vaccine.
• Booster study: Previous vaccination with any coronavirus vaccine outside of this study.
• Receipt of medications intended to prevent COVID-19.
• Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
• Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• Previous participation in other studies involving study intervention containing lipid nanoparticles.
• Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Additional Exclusion Criteria for the Booster study:

• Current febrile illness (body temperature ≥100.4°F [≥38.0°C]) or other acute illness within 48 hours before study intervention administration.
• Receipt of any seasonal or pandemic influenza vaccine within 14 days, or any other nonstudy vaccine within 28 days, before or after study intervention administration.
• Receipt of short-term (<14 days) systemic corticosteroids. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Contacts and Locations

Locations

United States, California

Kaiser Permanente Oakland

Oakland, California, United States, 94611

United States, Connecticut

Clinical Research Consulting

Milford, Connecticut, United States, 06460

United States, Florida

Indago Research & Health Center, Inc

Hialeah, Florida, United States, 33012

Research Centers of America

Hollywood, Florida, United States, 33024

Clinical Neuroscience Solutions

Orlando, Florida, United States, 32801

United States, Georgia

Clinical Research Atlanta

Stockbridge, Georgia, United States, 30281

United States, Hawaii

East-West Medical Research Institute

Honolulu, Hawaii, United States, 96814

United States, Idaho

Solaris Clinical Research

Meridian, Idaho, United States, 83646

United States, Kentucky

Kentucky Pediatric/Adult Research

Bardstown, Kentucky, United States, 40004

United States, New Jersey

Amici Clinical Research LLC

Raritan, New Jersey, United States, 08869

United States, North Carolina

Accellacare - Wilmington

Wilmington, North Carolina, United States, 28401

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45206

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229-3039

United States, Texas

Texas Center for Drug Development, Inc.

Houston, Texas, United States, 77081

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States, 78229

Martin Diagnostic Clinic

Tomball, Texas, United States, 77375

United States, Utah

J. Lewis Research, Inc. / Foothill Family Clinic South

Salt Lake City, Utah, United States, 84121

Sponsors and Collaborators

BioNTech SE

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: BioNTech SE
• ClinicalTrials.gov Identifier: NCT04713553
• Other Study ID Numbers: C4591017
• First Posted: January 19, 2021
• Last Update Posted: February 23, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioNTech SE:

COVID-19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine; BNT162b2; BNT162B2.1.B.351

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases