Clinical trial NCT04949490: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
SARS-CoV-2 Infection
Keywords: Infections, Respiratory
Virus Diseases
Infection Viral
Vaccine Adverse Reaction
RNA Virus Infections
Protection Against COVID-19 and Infections With SARS-CoV-2
Prevention of COVID-19 disease
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2021-07-02
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Up to 26 weeks after the first IMP injection
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: 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
timeFrame: 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 outcomes:
measure: Neutralizing Antibody Titers From Reference Strain and SARS-CoV-2 Variant B.1.351
timeFrame: 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).
measure: Antibody Titers (ELISA) to Recombinant S1 and RBD Protein Derived From Reference and SARS-CoV-2 Variant B.1.351
timeFrame: 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).
measure: SARS-CoV-2 Functional Cross-neutralization (GMT Ratios) of Variant B.1.351 to Reference Strain
timeFrame: Up to 26 weeks after the first IMP injection (Dose 1)
measure: Neutralizing Antibody Titers (Reference Strain) Derived From SARS-CoV-2
timeFrame: From baseline (Day 1 of Dose 1) up to 26 weeks after Dose 2
measure: Antibody Titers (ELISA) (Reference Strain) to Recombinant S1 and RBD Protein Derived From SARS-CoV-2
timeFrame: From baseline (Day 1 of Dose 1) up to 26 weeks after Dose 2
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: CRS Clinical Research Services Berlin GmbH
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt, Infectiology
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Clinical Pharmacology
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References:
citation: 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.