Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants

• ClinicalTrials.gov Identifier: NCT05004181
• Recruitment Status: Recruiting
• First Posted: August 13, 2021
• Last Update Posted: June 16, 2022
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: August 5, 2021
• First Posted Date: August 13, 2021
• Last Update Posted Date: June 16, 2022
• Actual Study Start Date: August 25, 2021
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2022)

• Percentage of participants reporting local reactions at the injection site [ Time Frame: up to 7 days after each dose ]
  Local reactions (pain, tenderness, erythema/redness, induration/swelling).
• Percentage of participants reporting systemic events [ Time Frame: up to 7 days after each dose ]
  Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain).
• Percentage of participants reporting adverse events (AEs) [ Time Frame: Dose 1 to 1 month after the last dose ]
• Percentage of participants reporting serious adverse events (SAEs) [ Time Frame: Dose 1 to 6 months after the last dose ]
• Part B - Geometric mean ratio (GMR) of B.1.1.7 [ Time Frame: 1 month ]
  GMR of B.1.1.7 neutralizing titers (NT) 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in Seroresponse (SR) to B.1.1.7 [ Time Frame: 1 month ]
  The difference in SR to B.1.1.7 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - The difference in SR to B.1.617.2 [ Time Frame: 1 month ]
  The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.1.7 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.617.2 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in SR to B.1.1.7 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in SR to B.1.617.2 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02/C4591001 trial [ Time Frame: 1 month ]
• Part C - GMR of B.1.1.529 NT 1 month after one dose of BNT162b2 (B.1.1.529) in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection to those at 1 month after one dose of BNT162b2 for Cohorts 7 and 8. [ Time Frame: 1 month ]
• Part C - The difference in SR of B.1.1.529 NT 1 month after one dose of BNT162b2 (B.1.1.529) in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection to those at 1 month after one dose of BNT162b2 for Cohorts 7 and 8. [ Time Frame: 1 month ]

Original Primary Outcome Measures (submitted: August 5, 2021)

• Percentage of participants reporting local reactions at the injection site [ Time Frame: up to 7 days after each dose ]
  Local reactions (pain, tenderness, erythema/redness, induration/swelling).
• Percentage of participants reporting systemic events [ Time Frame: up to 7 days after each dose ]
  Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain).
• Percentage of participants reporting adverse events (AEs) [ Time Frame: Dose 1 to 1 month after the last dose ]
• Percentage of participants reporting serious adverse events (SAEs) [ Time Frame: Dose 1 to 6 months after the last dose ]
• Part B - Geometric mean ratio (GMR) of B.1.1.7 [ Time Frame: 1 month ]
  GMR of B.1.1.7 neutralizing titers (NT) 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in Seroresponse (SR) to B.1.1.7 [ Time Frame: 1 month ]
  The difference in SR to B.1.1.7 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - The difference in SR to B.1.617.2 [ Time Frame: 1 month ]
  The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.
• Part B - The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.1.7 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - GMR of B.1.617.2 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in SR to B.1.1.7 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
• Part B - The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]

Current Secondary Outcome Measures (submitted: April 14, 2022)

• Part A - Geometric mean titer (GMT) [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT.
• Part A - Geometric mean fold rises (GMFR) from before vaccination to each subsequent time point after vaccination [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
• Part A - SR in terms of NT at each post vaccination time point [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
• Part B - GMT - B.1.1.7 + B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants). GMTs for SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) and dose 2 of BNT162b2.
• Part B - GMT - B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants). GMTs for SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.617.2) and dose 2 of BNT162b2.
• Part B - GMT - B.1.1.7 + B.1.617.2 to the reference strain [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-naïve participants). GMTs for SRs of VOCs and reference strain NT 1 month after dose 2 of BNT162b2 (B.1.1.7 + B.1.617.2) to the reference strain NT 1 month after the dose 2 of BNT162b2.
• Part C - GMT - B.1.1.529 or BNT162b2 or a post SARS-CoV-2 infection [ Time Frame: Day 1 to Day 360 ]
  VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the study start for Cohorts 7, 8, and 9, and 6 and 12 months after the study start for Cohorts 7 and 8.

Original Secondary Outcome Measures (submitted: August 5, 2021)

• Part A - Geometric mean titer (GMT) [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT.
• Part A - Geometric mean fold rises (GMFR) from before vaccination to each subsequent time point after vaccination [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
• Part A - SR in terms of NT at each post vaccination time point [ Time Frame: Day 1 to Day 360 ]
  For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
• Part B - GMT - B.1.1.7 + B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants). GMTs for SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) and dose 2 of BNT162b2.
• Part B - GMT - B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants). GMTs for SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.617.2) and dose 2 of BNT162b2.
• Part B - GMT - B.1.1.7 + B.1.617.2 to the reference strain [ Time Frame: Day 1 to Day 360 ]
  VOC and reference strain NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-naïve participants). GMTs for SRs of VOCs and reference strain NT 1 month after dose 2 of BNT162b2 (B.1.1.7 + B.1.617.2) to the reference strain NT 1 month after the dose 2 of BNT162b2.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants
• Official Title: A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects
• Brief Summary: This trial consists of three parts, Part A, Part B, and Part C, and will evaluate the safety and immunogenicity of a third booster injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who have received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It will also evaluate the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who have not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection will be evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant.
• Detailed Description: Trial participants in Part A will be assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B will be assigned to one of 3 cohorts (Cohort 1, 4 and 6). Trial participants in Part C will be randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• SARS-CoV2 Infection
• Covid19
• SARS-CoV-2 Acute Respiratory Disease
• SARS (Disease)

Intervention

• Biological: BNT162b2
  Intramuscular (IM)
• Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
  Intramuscular (IM)
• Biological: BNT162b2 (B.1.1.7)
  Intramuscular (IM)
• Biological: BNT162b2 (B.1.617.2)
  Intramuscular (IM)
• Biological: BNT162b2 (B.1.1.529)
  Intramuscular (IM)
• Other: Observational
  No vaccination within 3 months after Visit 1.

Study Arms

• Experimental: Part A - Cohort 1: 18 to 55 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
• Experimental: Part A - Cohort 2: 18 to 55 years of age
  Participants will receive 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
• Experimental: Part A - Cohort 3: 18 to 55 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.1.7) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7)
• Experimental: Part A - Cohort 4: 18 to 55 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.617.2)
• Experimental: Part A - Cohort 5: 18 to 55 years of age
  Participants will receive 1 dose of BNT162b2 of 30 µg.
  Intervention: Biological: BNT162b2
• Experimental: Part A - Cohort 6: 18 to 55 years of age
  Participants will receive 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
• Experimental: Part B - Cohort 1: 18 to 85 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
• Experimental: Part B - Cohort 4: 18 to 85 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.617.2)
• Experimental: Part B - Cohort 6: 18 to 85 years of age
  Participants will receive 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
• Experimental: Part C - Cohort 7: 18 to 85 years of age
  Participants will receive 1 dose of BNT162b2 (B.1.1.529) of 30 µg.
  Intervention: Biological: BNT162b2 (B.1.1.529)
• Experimental: Part C - Cohort 8: 18 to 85 years of age
  Participants will receive 1 dose of BNT162b2 of 30 µg.
  Intervention: Biological: BNT162b2
• Part C - Cohort 9: 18 to 85 years of age
  Participants will receive no vaccination within 3 months after Visit 1.
  Intervention: Other: Observational

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 14, 2022): 1655
• Original Estimated Enrollment (submitted: August 5, 2021): 1245
• Estimated Study Completion Date: September 2023
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
• Volunteers who at the time of consent are:
• Part A: 18 to 55 years old.
• Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
• For Cohorts 1 to 5: In Part A, who have received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who are currently enrolled in the Phase III BNT162-02 / C4591001 trial, have already been unblinded, and have previously received two doses of BNT162b2 at least 6 months earlier can be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the BNT162-02 / C4591001 trial is mandatory). At enrollment into Part B of this trial, their participation in the BNT162-02 / C4591001 trial will be terminated. Participants should have not experienced COVID-19 based on medical history.
• For Cohort 6: Are COVID-19 vaccine-naïve and have not experienced COVID-19 based on their medical history.
• Are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
• Are overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).

Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, can be included.

Note: Volunteers who had hepatitis C (HCV) infection, but have completed curative treatment based on the medical history can be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history cannot be included.

• Agree not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
• Women of childbearing potential (WOCBP) must test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
• WOCBP must agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
• WOCBP must confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
• WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
• Men who are sexually active with a WOCBP and have not had a vasectomy must agree to use a highly effective form of contraception with their female partner of childbearing potential starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
• Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
• For Part C, Cohorts 7, 8, and 9: have received two or three documented doses of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 on (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections) that is documented with a result from a nucleic acid amplification-based test (NAAT) for SARS-CoV-2.

Exclusion Criteria:

• Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
• Any bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, make the participant inappropriate for the trial.
• Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
• Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias.
• History of COVID-19 and/or 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) evidence of prior infection with SARS CoV 2 at screening (Visit 0).

Note: not applicable for Part C.

• History of Guillain-Barré syndrome.
• Known or suspected immunodeficiency.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
• History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
• Have received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).

Note: not applicable for Part C.

• Have received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
• Have received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard or care vaccinations should be planned with the trial IMP administrations in mind.
• 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), e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
• Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
• Participation in other trials involving IMP within 28 days or 5 half-lives (whichever is longer) prior to Visit 1 and/or during trial participation, besides participation in trials with BNT162b2.
• Are pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP treatment.
• Are vulnerable individuals as per International Conference on Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
• For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines and/or vaccination with any COVID-19 vaccine after SARS-CoV-2 infection from January 2022 on (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

• Listed Location Countries: Germany, South Africa, Turkey, United States

Administrative Information

• NCT Number: NCT05004181
• Other Study ID Numbers: BNT162-17; 2021-003458-22 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: Same as current
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: June 2022