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

Inclusion Criteria

• •Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
• •Volunteers who at the time of consent were:
• •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 had 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 were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
• •For Cohort 6: Were COVID-19 vaccine-naïve and had not experienced COVID-19 based on their medical history.
• •Were willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
• •Were 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, could be included.
• •Note: Volunteers who had hepatitis C (HCV) infection, but had completed curative treatment based on the medical history could be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history could not be included.
• •Agreed 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) had to test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
• •WOCBP had to 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 had to confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
• •WOCBP had to 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 had not had a vasectomy had to 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 had to 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: Had 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 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
• •Note: The interval between the last COVID-19 RNA-based vaccine administered and randomization should have been \>4 months. The latest prior diagnosed SARS-CoV-2 infection should have been at least 2 months before randomization. The latest SARS-CoV-2 infection should have been documented with a result from a NAAT (as a preferable option). In case no historic NAAT result was available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening was sufficient.