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

This is an interventional prevention trial for SARS-CoV2 Infection Read More

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 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 be >4 months. The latest prior diagnosed SARS-CoV-2 infection should be at least 2 months before randomization. The latest SARS-CoV-2 infection should be documented with a result from a NAAT (as a preferable option). In case no historic NAAT result is available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening will be sufficient.

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.
• For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after 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).