A Trial Investigating the Safety and Effects of One or Two Additional Doses of Comirnaty or One Dose of BNT162b2s01 in BNT162-01 or BNT162-04 Trial Subjects

A Phase II, Open-label, Rollover Trial to Evaluate the Safety and Immunogenicity of One or Two Boosting Doses of Comirnaty or One Dose of BNT162b2s01 in BNT162-01 Trial Subjects, or Two Boosting Doses of Comirnaty in BNT162-04 Trial Subjects

Trial to evaluate the safety and immunogenicity of one or two boosting doses of Comirnaty or one dose of BNT162b2s01 (Variant of concern [VOC] strain B.1.351) in BNT162-01 trial participants, or two boosting doses of Comirnaty in BNT162-04 trial participants.

Trial participants from BNT162-01 who received two injections of 30 μg Comirnaty were randomized 2:1 to one booster injection (BNT162b2s01: Comirnaty). Trial participants in either the trial BNT162-01 or BNT162-04 who did not receive the full two vaccinations of 30 μg Comirnaty were offered two injections of 30 μg Comirnaty as per the conditional marketing authorization. All potential rollover volunteers must enroll in this trial within less than 18 months of their last injection of a BNT162 candidate vaccine in the parent BNT162-01 or BNT162-04 trials.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: BNT162b2s01; Biological: BNT162b2

Detailed Description

Group A trial participants were randomized 2:1 to BNT162b2s01:Comirnaty. Group B trial participants were allocated to trial treatment without active randomization and selected participants were asked to participate in the detailed immunogenicity assessment based on their parent trial cohort.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • CRS Clinical Research Services Berlin GmbH
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt, Infectiology
  • Heidelberg, Germany, 69117
    • University Hospital Heidelberg, Clinical Pharmacology
  • Mannheim, Germany, 68167
    • CRS Clinical Research Services Mannheim GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
• Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (including those requested by the German and federal Governments, e.g., to follow good practices to reduce chances of spreading COVID 19), and other requirements of the trial.
• Have received BNT162 vaccine candidates in the BNT162-01 or BNT162-04 trials.
• Remained overall healthy (i.e., has not medically deteriorated significantly since participation in the parent trial, is not anticipated to die in the next 26 weeks, and is able to provide blood as specified by the trial without anticipated, deleterious medical consequences) in the clinical judgment of the investigator based on medical history and physical examination. Screening clinical laboratory tests are to assess the participants' "new baseline" unless required for eligibility. Note: in particular, caution should be used with a subject who has a history of cardiovascular disease, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmia.
• Agreed not to enroll in another trial of an IMP, starting after Visit 0 and continuously until Visit 5 (Day 50).
• Less than 18 months have passed since their last IMP injection in their parent trial.
• If they received 30 μg Comirnaty twice in the BNT162-01 trial, Visit 1 in this trial is ≥24 weeks after their last IMP injection, unless the subject is a Cohort 13 transplant subject of the BNT162-01 trial.
• If they received any other BNT162 vaccine candidate than Comirnaty in the BNT162-01 or BNT162-04 trial or are a Cohort 13 transplant subject, Visit 1 in this trial is ≥12 weeks after their last IMP injection.
• Have not been diagnosed with SARS-CoV-2 infection in the 12 weeks prior to day 1 (baseline). Participants who screen-fail on this criterion may be rescreened.

Exclusion Criteria:

• Have received any SARS-CoV-2 vaccine outside of the BNT162-01 or BNT162-04 trials.
• Have had a known allergy, hypersensitivity, or intolerance to the planned IMP including any excipients of the IMP.
• Have had a current febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours prior to day 1/IMP injection in this trial. Participants who screen-fail on this criterion may be rescreened.
• Have received a live or live attenuated vaccine within 30 days prior to day 1/IMP injection, or any other vaccination within 14 days prior to day 1/IMP injection. Participants who screen-fail on this criterion may be rescreened.
• Have had an ongoing AE assessed as related to any BNT162-01 or BNT162-04 trial vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A, BNT162b2s01 30 μg (1 dose); Trial participants from BNT162-01 (excluding transplant participants from Cohort 13) who received two injections of 30 μg BNT162b2 (Comirnaty) in the parent trial received one booster injection of BNT162b2s01 on Day 1. Day 1 (baseline in this trial) must have occurred ≥24 weeks after the last BNT162b2 (Comirnaty) injection in the parent BNT162-01 trial.	Biological: BNT162b2s01; intramuscular (IM) injection
Experimental: Group A, BNT162b2 30 μg (1 dose); Trial participants from BNT162-01 (excluding transplant participants from Cohort 13) who received two injections of 30 μg BNT162b2 (Comirnaty) in the parent trial received one booster injection of BNT162b2 (Comirnaty) on Day 1. Day 1 (baseline in this trial) must have occurred ≥24 weeks after the last BNT162b2 (Comirnaty) injection in the parent BNT162-01 trial.	Biological: BNT162b2; IM injection; Other Names: Comirnaty
Experimental: Group B, BNT162b2 30 μg (2 doses); Trial participants in either the trial BNT162-01 (excluding transplant participants from Cohort 13) or BNT162-04 who did not receive the full two vaccinations of 30 μg BNT162b2 (Comirnaty) in the respective parent trial were offered two injections of 30 μg BNT162b2 (Comirnaty) as per the conditional marketing authorization on Day 1 and Day 21. Day 1 (baseline in this trial) must have occurred ≥12 weeks after receiving the last BNT162 candidate vaccine in the respective parent BNT162-01 or BNT162-04 trial.	Biological: BNT162b2; IM injection; Other Names: Comirnaty
Experimental: Group B transplant subjects, BNT162b2 30 μg (2 doses); Transplant trial participants from Cohort 13 of the trial BNT162-01 received one injection of 30 μg BNT162b2 (Comirnaty) on Day 1 which was followed 3 to 7 months afterward by a second injection of BNT162b2 (Comirnaty). Day 1 (baseline in this trial) must have occurred ≥12 weeks after receiving the last BNT162 candidate vaccine in the parent BNT162-01 trial.	Biological: BNT162b2; IM injection; Other Names: Comirnaty

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number and Percentage of Participants in Each Treatment Group With at Least One Serious Adverse Event (SAE) or Adverse Events of Special Interest (AESIs)	For treatment-emergent SAEs and AESIs (TESAEs, TEAESIs), the data refers to the interval "Dose 1 up to 28 days after Dose 1". For other SAEs and AESIs, the data refers to the interval "Dose 1 up to 26 weeks after Dose 1". A TESAE/TEAESI is defined as any SAE/AESI with an onset after the first IMP dose or worsened after the first IMP dose (if the SAE/AESI was present before the first administration of IMP). SAEs/AESIs with an onset date more than 28 days after the last administration of IMP will be considered as TESAE/TEAESI only if assessed as related to IMP by the investigator. Participants of the Group B immunology subset are also included in the respective Group B arms and therefore counted in more than one arm/group. Overall a total of 137 participants were enrolled into this study (including the Group B immunology subset participants).	Up to 26 weeks after the first IMP injection
The Number and Percentage of Participants With Solicited Local Reactions at the Injection Site Recorded up to 7 Days After Each IMP Injection for Group A and for a Selected Subset (Immunology Subset) of Group B Participants.	Local reactions (pain, tenderness, erythema/redness, induration/swelling) were graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of local reactions was based on the participant's assessments via daily solicited reports in the participant diaries. Participants of the Group B immunology subset are part of the Group B. The 'Total' arms include all participants from the respective Group A and Group B immunology subset arms presented.	Group A: From Day 1 to Day 8; For Group B (except transplant participants): From Day 1 to Day 8 for Dose 1, and from Day 22 to Day 29 for Dose 2. For Group B transplant participants: From Day 1 to Day 8 for Dose 1, and up to 7 days after Dose 2.
The Number and Percentage of Participants With Solicited Systemic Reactions Recorded up to 7 Days After Each IMP Injection for Group A and for a Selected Subset (Immunology Subset) of Group B Participants.	Systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills and fever) were graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments via daily solicited reports in the participant diaries. Participants of the Group B immunology subset are part of the Group B. The 'Total' arms include all participants from the respective Group A and Group B immunology subset arms presented.	Group A: From Day 1 to Day 8; For Group B (except transplant participants): From Day 1 to Day 8 for Dose 1, and from Day 22 to Day 29 for Dose 2. For Group B transplant participants: From Day 1 to Day 8 for Dose 1, and up to 7 days after Dose 2.
The Number and Percentage of Participants With at Least One Unsolicited TEAE Occurring up to 28 Days After IMP Injection in Each Treatment Group for Group A and for a Selected Subset (Immunology Subset) of Group B Participants	A TEAE is defined as any AE with an onset after the first IMP injection or worsened after the first IMP injection (if the AE was present before the first administration of IMP). AEs with an onset date more than 28 days after the last administration of IMP will be considered as treatment-emergent only if assessed as related to IMP by the investigator. Participants of the Group B immunology subset are part of the Group B. The 'Total' arms include all participants from the respective Group A and Group B immunology subset arms presented.	Group A: Up to 28 days after Dose 1. Group B: Up to 28 days after Dose 1 and up to 28 days after Dose 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutralizing Antibody Titers From Reference Strain and SARS-CoV-2 Variant B.1.351	For Group A participants and Group B participants (except transplant subjects). Non-transplant participants of the Group B immunology subset are also part of the respective Group B arm and therefore occurring in more than one arm/group. The 'Total' arm for Group A include all participants from the Group A arms/groups.	Group A: At baseline (Day 1) and Day 8 and at Week 4 Day 29), Week 12 (Day 85), and Week 26 (Day 182). Group B: At baseline (Day 1) and Day 8 and at Week 3 (Day 22), Week 4 (Day 29), Week 7 (Day 50), Week 12 (Day 85), and Week 26 (Day 182).
Antibody Titers (ELISA) to Recombinant S1 and RBD Protein Derived From Reference and SARS-CoV-2 Variant B.1.351	For Group A participants and Group B participants (except transplant subjects). Non-transplant participants in the Group B immunology subset arm are also part of the respective Group B arm and therefore occurring in more than one arm/group. The 'Total' arm for Group A include all participants from the Group A arms/groups.	Group A: At baseline (Day 1) and Day 8 and at Week 4 Day 29), Week 12 (Day 85), and Week 26 (Day 182). Group B: At baseline (Day 1) and Day 8 and at Week 3 (Day 22), Week 4 (Day 29), Week 7 (Day 50), Week 12 (Day 85), and Week 26 (Day 182).
SARS-CoV-2 Functional Cross-neutralization (GMT Ratios) of Variant B.1.351 to Reference Strain	For Group A only. The geometric mean titer (GMT) ratio is calculated as the GMT of reference divided by the GMT of variant B.1.351. The 'Total' arm for Group A include all participants from the two Group A arms/groups.	Up to 26 weeks after the first IMP injection (Dose 1)
Neutralizing Antibody Titers (Reference Strain) Derived From SARS-CoV-2	For Group B transplant subjects, assessed at baseline (Day 1 of Dose 1) and then Day 8, Weeks 4, 12, and 26 post Dose 1, and at Dose 2 (Day 1) and the Day 8, Weeks 4, 12, and 26 post Dose 2. Because the 11 participants of the arm 'Group B Immunology Subset Transplant Participants' are the same 11 participants of the arm 'Group B Immunology Subset Transplant Participants', data is not presented for this arm to avoid duplication of data.	From baseline (Day 1 of Dose 1) up to 26 weeks after Dose 2
Antibody Titers (ELISA) (Reference Strain) to Recombinant S1 and RBD Protein Derived From SARS-CoV-2	For Group B transplant subjects, assessed at baseline (Day 1 of Dose 1) and then Day 8, Weeks 4, 12, and 26 post Dose 1, and at Dose 2 (Day 1) and the Day 8, Weeks 4, 12, and 26 post Dose 2. Because the 11 participants of the arm 'Group B Immunology Subset Transplant Participants' are the same 11 participants of the arm 'Group B Immunology Subset Transplant Participants', data is not presented for this arm to avoid duplication of data.	From baseline (Day 1 of Dose 1) up to 26 weeks after Dose 2

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Publications and helpful links

General Publications

• Quandt J, Muik A, Salisch N, Lui BG, Lutz S, Kruger K, Wallisch AK, Adams-Quack P, Bacher M, Finlayson A, Ozhelvaci O, Vogler I, Grikscheit K, Hoehl S, Goetsch U, Ciesek S, Tureci O, Sahin U. Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes. Sci Immunol. 2022 Sep 16;7(75):eabq2427. doi: 10.1126/sciimmunol.abq2427. Epub 2022 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): April 14, 2022
• Study Completion (Actual): September 16, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Virus Diseases; Infection Viral; RNA Virus Infections; Vaccine Adverse Reaction; Infections, Respiratory; Prevention of COVID-19 disease; Protection Against COVID-19 and Infections With SARS-CoV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: BNT162-14; 2021-002387-50 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No