Clinical trial NCT04713553: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2 Infection
COVID-19
Keywords: COVID-19
Coronavirus
Vaccine
SARS-CoV-2
RNA Vaccine
BNT162b2
BNT162B2.1.B.351
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2021-01-19
Enrollment: 1574
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


Eligibility 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.

Primary outcomes:
measure: Geometric Mean Ratios (GMRs) of Full-Length S-Binding Immunoglobulin G (IgG) Concentrations Between Individual US Lots 1, 2, and 3 at 1 Month After Dose 2: Primary Study
timeFrame: 1 Month after Dose 2
measure: Geometric Mean Ratios (GMRs) of Full-Length S-Binding IgG Concentrations Between EU Lot and Pooled US Lots at 1 Month After Dose 2: Primary Study
timeFrame: 1 Month after Dose 2
measure: Geometric Mean Ratios (GMRs) of SARS-CoV-2 Neutralizing Titers Between 20-microgram Dose and 30-microgram Dose at 1 Month After Dose 2: Primary Study
timeFrame: 1 Month after Dose 2
measure: Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Primary Study
timeFrame: Within 7 days after Dose 1
measure: Percentage of Participants With Local Reactions Within 7 Days After Dose 2: Primary Study
timeFrame: Within 7 days after Dose 2
measure: Percentage of Participants With Local Reactions Within 7 Days After Any Dose: Primary Study
timeFrame: Within 7 days after any dose
measure: Percentage of Participants With Local Reactions Within 7 Days After Dose 3: Booster Study
timeFrame: Within 7 days after Dose 3
measure: Percentage of Participants With Systemic Events Within 7 Days After Dose 1: Primary Study
timeFrame: Within 7 days after Dose 1
measure: Percentage of Participants With Systemic Events Within 7 Days After Dose 2: Primary Study
timeFrame: Within 7 days after Dose 2
measure: Percentage of Participants With Systemic Events Within 7 Days After Any Dose: Primary Study
timeFrame: Within 7 days after any dose
measure: Percentage of Participants With Systemic Events Within 7 Days After Dose 3: Booster Study
timeFrame: Within 7 days after Dose 3
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 2: Primary Study
timeFrame: Day 1 of Dose 1 up to 1 Month after Dose 2 (for a maximum of 2 months)
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Dose 3 to 1 Month After Dose 3: Booster Study
timeFrame: From Dose 3 to 1 Month after Dose 3 (for a maximum of 35 days)
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Reference-strain at Baseline: Booster Study
timeFrame: Baseline (prior to Dose 1 of Primary study)
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Reference-strain 1 Month After Dose 2: Booster Study
timeFrame: 1 Month after Dose 2 of primary study
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Reference-strain Before Dose 3: Booster Study
timeFrame: Before Dose 3
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Reference-strain 1 Week After Dose 3: Booster Study
timeFrame: 1 Week after Dose 3
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Reference-strain 1 Month After Dose 3: Booster Study
timeFrame: 1 Month after Dose 3
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 B.1.351-strain at Baseline: Booster Study
timeFrame: Baseline (prior to Dose 1 of Primary study)
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 B.1.351-strain 1 Month After Dose 2: Booster Study
timeFrame: 1 Month after Dose 2 of primary study
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 B.1.351-strain Before Dose 3: Booster Study
timeFrame: Before Dose 3
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 B.1.351-strain 1 Week After Dose 3: Booster Study
timeFrame: 1 Week after Dose 3
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 B.1.351-strain 1 Month After Dose 3: Booster Study
timeFrame: 1 Month after Dose 3
measure: Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels at Baseline: Booster Study
timeFrame: Baseline (prior to Dose 1 of Primary study)
measure: Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels 1 Month After Dose 2: Booster Study
timeFrame: 1 Month after Dose 2 of primary study
measure: Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels Before Dose 3: Booster Study
timeFrame: Before Dose 3
measure: Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels 1 Week After Dose 3: Booster Study
timeFrame: 1 Week after Dose 3
measure: Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels 1 Month After Dose 3: Booster Study
timeFrame: 1 Month after Dose 3
measure: Geometric Mean Fold Rises (GMFRs) in Full-length S-binding IgG Levels From 1 Month After Dose 2 to 1 Week After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Week after Dose 3
measure: Geometric Mean Fold Rises (GMFRs) in Full-length S-binding IgG Levels From 1 Month After Dose 2 to 1 Month After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Month after Dose 3
measure: Geometric Mean Fold Rises (GMFRs) in Full-length S-binding IgG Levels Before Dose 3 to 1 Week After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Week after Dose 3
measure: Geometric Mean Fold Rises (GMFRs) in Full-length S-binding IgG Levels Before Dose 3 to 1 Month After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Month after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 Reference-strain From 1 Month After Dose 2 to 1 Week After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Week after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 Reference-strain From 1 Month After Dose 2 to 1 Month After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Month after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 Reference-strain Before Dose 3 to 1 Week After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Week after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 Reference-strain Before Dose 3 to 1 Month After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Month after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 B.1.351-strain From 1 Month After Dose 2 to 1 Week After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Week after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 B.1.351-strain From 1 Month After Dose 2 to 1 Month After Dose 3: Booster Study
timeFrame: From 1 Month after Dose 2 to 1 Month after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 B.1.351-strain Before Dose 3 to 1 Week After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Week after Dose 3
measure: Geometric Mean Fold Rise (GMFRs) in SARS-CoV-2 B.1.351-strain Before Dose 3 to 1 Month After Dose 3: Booster Study
timeFrame: Before Dose 3 to 1 Month after Dose 3
measure: Percentage of Participants With Seroresponse to Reference Strain at 1 Month After Dose 2: Booster Study
timeFrame: 1 Month after Dose 2
measure: Percentage of Participants With Seroresponse to Reference Strain Before Dose 3: Booster Study
timeFrame: Before Dose 3
measure: Percentage of Participants With Seroresponse to Reference Strain 1 Week After Dose 3: Booster Study
timeFrame: 1 Week after Dose 3
measure: Percentage of Participants With Seroresponse to Reference Strain 1 Month After Dose 3: Booster Study
timeFrame: 1 Month after Dose 3
measure: Percentage of Participants With Seroresponse to B.1.351 Variant Strain at 1 Month After Dose 2: Booster Study
timeFrame: 1 Month after Dose 2
measure: Percentage of Participants With Seroresponse to B.1.351 Variant Strain Before Dose 3: Booster Study
timeFrame: Before Dose 3
measure: Percentage of Participants With Seroresponse to B.1.351 Variant Strain 1 Week After Dose 3: Booster Study
timeFrame: 1 Week after Dose 3
measure: Percentage of Participants With Seroresponse to B.1.351 Variant Strain 1 Month After Dose 3: Booster Study
timeFrame: 1 Month after Dose 3
Secondary outcomes:
measure: Geometric Mean Concentrations (GMCs) of Full-Length S-Binding IgG Levels at Baseline and 1 Month After Dose 2 for 30 mcg Dose of BNT162b2: Primary Study
timeFrame: Baseline (before Dose 1), 1 Month after Dose 2
measure: Geometric Mean Fold Rises (GMFRs) in Full-Length S-Binding lgG Levels From Baseline to 1 Month After Dose 2 for 30 mcg Dose of BNT162b2: Primary Study
timeFrame: From Baseline (before Dose 1) up to 1 Month after Dose 2
measure: Geometric Mean Titers (GMT) of SARS-CoV-2 Neutralizing Titers at Baseline and 1 Month After Dose 2 for 20 mcg and 30 mcg Dose of BNT162b2 From US Lot 1: Primary Study
timeFrame: Baseline (before Dose 1), 1 Month after Dose 2
measure: Geometric Mean Fold Rises (GMFRs) in SARS-CoV-2 Neutralizing Titers From Baseline to 1 Month After Dose 2 for 20 mcg and 30 mcg Dose of BNT162b2 From US Lot 1: Primary Study
timeFrame: From Baseline (before Dose 1) up to 1 Month after Dose 2
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Milford
country: United States
facility: Clinical Research Consulting
state: Connecticut
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
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: Meridian
country: United States
facility: Solaris Clinical Research
state: Idaho
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research
state: Kentucky
city: Raritan
country: United States
facility: Amici Clinical Research LLC
state: New Jersey
city: Wilmington
country: United States
facility: Accellacare - Wilmington
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic South
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: