A Study to Evaluate Safety, Tolerability, & Immunogenicity of Multiple Formulations of BNT162b2 Against COVID-19 in Healthy Adults

A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE FORMULATIONS OF THE VACCINE CANDIDATE BNT162B2 AGAINST COVID 19 IN HEALTHY ADULTS 18 THROUGH 55 YEARS OF AGE

This study will compare the safety and tolerability of lyophilized BNT162b2 presented in single dose vials to those of frozen-liquid BNT162b2 in multidose vials and determine whether the immune response is noninferior. Separately, the study will also describe the safety and immunogenicity of frozen-liquid BNT162b2 with lipid nanoparticle size at the upper end of specification and ready to use BNT162b2 (the immediate manufacturing precursor to the lyophilate). Additionally, the study will describe the safety and immunogenicity of an additional dose of frozen liquid BNT162b2 to participants who already received the 2-dose schedule of lyophilized BNT162b2.

• 2-dose schedule (separated by 21 days)
• At a dose of 30µg (as studied in the Phase 2/3 study C4591001)
• In healthy adults 18 through 55 years of age
• The duration of the study for each participant will be approximately 2 months (3 visits in total)
• The study will be conducted in the United States

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: BNT162b2

• Study Type: Interventional
• Enrollment (Actual): 629
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/ Adult Research
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
  • New Jersey
    • Raritan, New Jersey, United States, 08869
      • Amici Clinical Research LLC
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare (formerly PMG Research of Wilmington, LLC)
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic
    • Tomball, Texas, United States, 77375
      • DM Clinical Research (Administrative and Storage Office only)
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female participants 18 - 55 years of age, inclusive, at Visit 1, (Day 1).
• 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. Note: Healthy participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrolment, can be included.
• Capable of giving personal signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in the protocol.
• For Dose 3: Participants who received BOTH doses of the lyophilized formulation of BNT162b2 as part of the initial study.

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(s).
• 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.
• Previous vaccination with any coronavirus vaccine.
• Receipt of medications intended to prevent COVID-19.
• Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
• 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 (LNPs).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lyophilized SDV	Biological: BNT162b2; Intramuscular injection
Experimental: Frozen liquid MDV (control for lyo SDV); Control for lyophilized SDV	Biological: BNT162b2; Intramuscular injection
Experimental: Frozen-liquid with LNP size at the upper end of specification	Biological: BNT162b2; Intramuscular injection
Experimental: RTU	Biological: BNT162b2; Intramuscular injection
Experimental: Frozen liquid MDV (given as third dose following a primary series of lyophilized BNT162b2); Additional vaccine dose, using the frozen-liquid formulation, offered to participants who originally received 2 doses of the lyophilized formulation of BNT162b2	Biological: BNT162b2; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Full-Length S-Binding IgG Concentrations of Lyophilized Formulation SDVs and Frozen-Liquid Formulation in MDVs 1 Month After Dose 2	GMTs of full-length S-binding IgG level for lyophilized formulation in SDVs and frozen-Liquid formulation in MDVs were reported in this outcome measure as geometric mean concentration (GMCs) in descriptive data section. GMC and 95 percent (%) confidence interval (CI) were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Geometric mean ratio (GMR) was calculated as ratios of GMCs of BNT162b2 30 mcg lyophilized SDV and frozen-liquid MDV. GMR are reported in the statistical analysis section.	1 Month after Dose 2
Percentage of Participants With Local Reactions Within 7 Days After Dose 1	Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after each vaccination.	Within 7 days after Dose 1
Percentage of Participants With Local Reactions Within 7 Days After Dose 2	Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after each vaccination.	Within 7 days after Dose 2
Percentage of Participants With Systemic Events Within 7 Days After Dose 1	Systemic events were reported using an electronic diary. Fever was defined as temperature >=38.0 degree Celsius (C). Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, and diarrhea after Dose 1 were reported.	Within 7 days after Dose 1
Percentage of Participants With Systemic Events Within 7 Days After Dose 2	Systemic events were reported using an electronic diary. Fever was defined as temperature >=38.0 degree C. Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, and diarrhea after Dose 2 were reported.	Within 7 days after Dose 2
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 2	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or that was considered to be an important medical event. AEs included all non-SAEs and SAEs. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.	Dose 1 up to 1 Month after Dose 2 (for approximately 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentrations (GMCs) of Full-length S-binding IgG Levels at Baseline: Part 1	GMCs of full-length S-binding IgG levels were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	Baseline (Before Dose 1 on Day 1)
Geometric Mean Fold Rises (GMFRs) in Full-length S-binding IgG Levels From Baseline to 1 Month After Dose 2: Part 1	GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 month after Dose 2 to the geometric mean concentration of IgG at Baseline. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	From Baseline (Before Dose 1 on Day 1) up to 1 Month after Dose 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs of Full-Length S-Binding IgG Concentrations of Frozen Liquid With LNP Size at Upper End of Specification and Frozen-Liquid Formulation in MDVs 1 Month After Dose 2	GMTs of full-length S-binding IgG level for frozen liquid with LNP size at upper end of specification relative to frozen-liquid formulation in MDVs were reported in this outcome measure as GMCs in descriptive data section. GMC and 95 % CI were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was calculated as ratios of GMCs of BNT162b2 30 mcg frozen liquid with LNP size at upper end of specification relative to frozen-liquid formulation in MDVs. GMR are reported in the statistical analysis section.	1 Month after Dose 2
GMCs of Full-length S-binding IgG Levels at Baseline and 1 Month After Dose 2: Part 2	GMCs of full-length S-binding IgG levels were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	Baseline (Before Dose 1 on Day 1), 1 Month after Dose 2
GMFRs in Full-length S-binding IgG Levels From Baseline to 1 Month After Dose 2: Part 2	GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 month after Dose 2 to the geometric mean concentration of IgG at Baseline. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	From Baseline (Before Dose 1 on Day 1) up to 1 Month after Dose 2
Percentage of Participants With Local Reactions Within 7 Days After Dose 3	Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after Dose 3.	Within 7 days after Dose 3
Percentage of Participants With Systemic Events Within 7 Days After Dose 3	Systemic events were reported using an electronic diary. Fever was defined as temperature >=38.0 degree Celsius (C). Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, and diarrhea after Dose 3 were reported.	Within 7 days after Dose 3
Number of Participants With AEs and SAEs From Dose 3 to 1 Month After Dose 3	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or that was considered to be an important medical event. AEs included all non-SAEs and SAEs. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.	Dose 3 up to 1 Month after Dose 3 (1 month)
GMFRs in Full-length S-binding IgG Levels From Before Dose 3 to 1 Month After Dose 3	GMFRs were defined as ratios of the geometric mean concentration of IgG from 1 month after Dose 3 to geometric mean concentration of IgG before Dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	From before Dose 3 to 1 Month after Dose 3
GMCs of Full-Length S-Binding IgG Levels at Baseline, 1 Month After Dose 2, Before Dose 3, and 1 Month After Dose 3	GMCs of full-length S-binding IgG levels were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	Baseline, 1 Month after Dose 2, before Dose 3, and 1 Month after Dose 3

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 2, 2021

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; Coronavirus; COVID-19; RNA Vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: C4591020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No