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

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

Official Title
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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

Conditions
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COVID-19, SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: BNT162b2s01
* Biological: BNT162b2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures. 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. Remain 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. Agree 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 a known allergy, hypersensitivity, or intolerance to the planned IMP including any excipients of the IMP. Have 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 an ongoing AE assessed as related to any BNT162-01 or BNT162-04 trial vaccine.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A, BNT162b2s01 30 µg (1 dose)<br>Trial participants from BNT162-01 (excluding transplant participants from Cohort 13) who received two injections of 30 μg BNT162b2 (Comirnaty) will receive one booster injection of BNT162b2s01 on Day 1. Day 1 (baseline in this trial) must occur ≥24 weeks after the last BNT162b2 (Comirnaty) injection in the parent BNT162-01 trial. | Biological: BNT162b2s01<br>* intramuscular (IM) injection<br>|
| Experimental: Group A, BNT162b2 30 µg (1 dose)<br>Trial participants from BNT162-01 (excluding transplant participants from Cohort 13) who received two injections of 30 μg BNT162b2 (Comirnaty) will receive one booster injection of BNT162b2 (Comirnaty) on Day 1. Day 1 (baseline in this trial) must occur ≥24 weeks after the last BNT162b2 (Comirnaty) injection in the parent BNT162-01 trial. | Biological: BNT162b2<br>* IM injection<br>* Other names: Comirnaty;|
| Experimental: Group B, BNT162b2 30 µg (2 doses)<br>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) will be 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 occur ≥12 weeks after receiving the last BNT162 candidate vaccine in the respective parent BNT162-01 or BNT162-04 trial. | Biological: BNT162b2<br>* IM injection<br>* Other names: Comirnaty;|
| Experimental: Group B transplant subjects, BNT162b2 30 µg (2 doses)<br>Transplant trial participants from Cohort 13 of the trial BNT162-01 will receive one injection of 30 μg BNT162b2 (Comirnaty) on Day 1 which will be followed 3 to 7 months afterward by a second injection of BNT162b2 (Comirnaty). Day 1 (baseline in this trial) must occur ≥12 weeks after receiving the last BNT162 candidate vaccine in the parent BNT162-01 trial. | Biological: BNT162b2<br>* IM injection<br>* Other names: Comirnaty;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants in each treatment group with at least one serious adverse event (SAE) or the proportion of adverse events of special interest (AESIs) | occurring up to 26 weeks after the first investigational medicinal product (IMP) injection. For all Group A and Group B participants. | up to 26 weeks after the first IMP injection | 
| The frequency of solicited local reactions (pain, tenderness, erythema/redness, induration/swelling) at the injection site recorded up to 7 days after each IMP injection | For Group A and for a selected subset of Group B participants. | up to 7 days after each IMP injection | 
| The frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue/tiredness, fever, chills, nausea, new or worsened muscle pain, new or worsening joint pain) recorded up to 7 days after each IMP injection | For Group A and for a selected subset of Group B participants. | up to 7 days after each IMP injection | 
| The proportion of participants with at least one unsolicited treatment emergent adverse event (TEAE) occurring up to 28 days after IMP injection in each treatment group | For Group A and for a selected subset of Group B participants. | up to 28 days after IMP injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody titers and antibody titers (ELISA) to recombinant S1 and receptor binding domain (RBD) protein derived from reference and SARS-CoV-2 variant B.1.351 will be assessed at baseline (Day 1) and then Day 8, Weeks 4, 12, and 26 | For Group A participants. | day 1 and day 8; weeks 4, 12, and 26 | 
| Neutralizing antibody titers and antibody titers (ELISA) to recombinant S1 and RBD protein derived from reference and SARS-CoV-2 variant B.1.351 will be assessed at baseline (Day 1) and then Day 8, Weeks 3, 4, 7, 12, and 26 | For Group B participants (except transplant subjects). | Day 1 and day 8; weeks 3, 4, 7, 12, and 26 | 
| SARS-CoV-2 functional cross-neutralization of variant B.1.351 to reference strain | For Group A only. | up to 26 weeks after the first IMP injection | 
| Neutralizing antibody titers and antibody titers (ELISA) to recombinant S1 and RBD protein derived from SARS-CoV-2 assessed at baseline 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 | For Group B transplant subjects. | From baseline (Day 1 of Dose 1) up to 26 weeks after Dose 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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