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

Sponsor
BioNTech SE (Industry)
Overall Status
Completed
CT.gov ID
NCT04713553
Collaborator
Pfizer (Industry)
1,530
17
7
5.2
90
17.4

Study Details

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
  • Biological: BNT162b2
  • Biological: BNT162b2.B.1.351
Phase 3

Study Design

Study Type:
Interventional
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 :
Feb 15, 2021
Actual Primary Completion Date :
Jul 22, 2021
Actual Study Completion Date :
Jul 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 [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 [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. [At 1 month after Dose 2]

    As measured at the central laboratory

  4. Percentage of participants reporting local reactions [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 [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 [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 [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). [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). [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). [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). [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. [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. [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). [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) [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) [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). [From baseline (before Dose 1) to 1 month after Dose 2]

    As measured at the central laboratory

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Site City State Country Postal Code
1 Kaiser Permanente Oakland Oakland California United States 94611
2 Clinical Research Consulting Milford Connecticut United States 06460
3 Indago Research & Health Center, Inc Hialeah Florida United States 33012
4 Research Centers of America Hollywood Florida United States 33024
5 Clinical Neuroscience Solutions Orlando Florida United States 32801
6 Clinical Research Atlanta Stockbridge Georgia United States 30281
7 East-West Medical Research Institute Honolulu Hawaii United States 96814
8 Solaris Clinical Research Meridian Idaho United States 83646
9 Kentucky Pediatric/Adult Research Bardstown Kentucky United States 40004
10 Amici Clinical Research LLC Raritan New Jersey United States 08869
11 Accellacare - Wilmington Wilmington North Carolina United States 28401
12 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45206
13 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229-3039
14 Texas Center for Drug Development, Inc. Houston Texas United States 77081
15 Clinical Trials of Texas, Inc. San Antonio Texas United States 78229
16 Martin Diagnostic Clinic Tomball Texas United States 77375
17 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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
BioNTech SE
ClinicalTrials.gov Identifier:
NCT04713553
Other Study ID Numbers:
  • C4591017
First Posted:
Jan 19, 2021
Last Update Posted:
Feb 23, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 23, 2022