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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04816669
• Other study ID #: C4591020
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2021
• Est. completion date: December 2, 2021

Study information

• Verified date: November 2022
• Source: BioNTech SE
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 629
• Est. completion date: December 2, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Biological:
• BNT162b2
Intramuscular injection

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Benchmark Research	Austin	Texas
United States	Kentucky Pediatric/ Adult Research	Bardstown	Kentucky
United States	Aventiv Research Inc	Columbus	Ohio
United States	University of Texas Medical Branch	Galveston	Texas
United States	Indago Research & Health Center, Inc	Hialeah	Florida
United States	Research Centers of America ( Hollywood )	Hollywood	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Jacksonville	Florida
United States	Solaris Clinical Research	Meridian	Idaho
United States	Meridian Clinical Research, LLC	Omaha	Nebraska
United States	Clinical Neuroscience Solutions	Orlando	Florida
United States	Amici Clinical Research LLC	Raritan	New Jersey
United States	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	DM Clinical Research (Administrative and Storage Office only)	Tomball	Texas
United States	Martin Diagnostic Clinic	Tomball	Texas
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Accellacare (formerly PMG Research of Wilmington, LLC)	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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)
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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

External Links

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