| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Protection against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV 2). |
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| E.1.1.1 | Medical condition in easily understood language |
| Prevention of infection with the Corona virus |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051905 |
| E.1.2 | Term | Coronavirus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10084510 |
| E.1.2 | Term | Coronavirus infections |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10084529 |
| E.1.2 | Term | 2019 novel coronavirus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary safety objectives in Part A
To describe:
- the safety profile of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) given as one or two booster doses to BNT162b2-experienced subjects, or as three doses to COVID-19 vaccine-naïve subjects.
- the safety profile of the monovalent vaccine BNT162b2 (B.1.1.7) given as one booster dose to BNT162b2-experienced subjects.
- the safety profile of the monovalent vaccine BNT162b2 (B.1.617.2) given as one booster dose to BNT162b2-experienced subjects.
- the safety profile of BNT162b2, given as one booster dose to BNT162b2-experienced subjects.
In Part B to describe:
- the safety profile of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) given as one booster dose to BNT162b2-experienced subjects, or as two doses to BNT162b2 naïve subjects.
- the safety profile of the monovalent vaccine BNT162b2 (B.1.617.2) given as one booster dose to BNT162b2-experienced subjects.
Part B and Part C check the protocol, characters limit |
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| E.2.2 | Secondary objectives of the trial |
Immunogenicity - Part A
To describe the immune response after one, two or three doses of BNT162b2 (B.1.1.7 + B.1.617.2), BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2), and BNT162b2.
BNT162b2-experienced subjects - Part B
To describe the immune response against the reference strain and VOCs after one dose of multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) vs two doses of BNT162b2.
To describe the immune response against the reference strain and VOCs after one dose of monovalent vaccine BNT162b2 (B.1.617.2) vs two doses of BNT162b2.
COVID-19 vaccine-naïve subjects- Part B
To describe the immune response against the reference strain and VOCs after three doses of multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2).
Full part B and Part C check the protocol, characters limit
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
2. Volunteers who at the time of consent are:
− Part A: 18 to 55 years old.
− Part B: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
- Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
3. For Cohorts 1 to 5: in Part A, 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. Subjects who are currently enrolled in the Phase III BNT162-02 / C4591001 trial, have already been unblinded, and have previously received two doses of BNT162b2 with Dose 2 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. Subjects should have not experienced COVID 19 based on medical history.
4. For Cohort 6: Are COVID 19 vaccine–naïve and have not experienced COVID 19 based on their medical history.
5. Are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
6. 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 ECG, and oral swab for NAAT-based 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.
7. Agree not to enroll in another trial of an IMP, starting after Visit 0 and continuously until the last planned visit in this trial.
8. Women of childbearing potential (WOCBP) must test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1. For a definition of “WOCBP”.
9. 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. For a definition of “highly effective form of contraception”.
10. WOCBP must confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0. For a definition of “acceptable form of contraception”.
11. 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.
12. 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.
13. Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
14. 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 SARSCoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening will be sufficient.
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| E.4 | Principal exclusion criteria |
1. Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
2. Any bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
3. 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 subject inappropriate for the trial.
4. 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.
5. Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease is not considered relevant for participation in this trial in the investigator's judgment.
6. History of COVID 19 and/or clinical (based on clinical confirmed 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.
7. History of Guillain-Barré syndrome.
8. Known or suspected immunodeficiency.
9. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
10. History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
11. Have received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses ~ 21 days apart).
Note: not applicable for Part C.
12. Have received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
13. 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.
14. 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, intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
15. Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
16. 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.
17. Are pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP Treatment.
18. Are vulnerable individuals as per 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.
19. For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines.
20. 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).
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety - Part A
• Local reactions (pain, tenderness, erythema/redness, induration/swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, nausea, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
Safety - Part B
• Local reactions (pain, tenderness, erythema/redness, induration/swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
Immunogenicity - BNT162b2-experienced subjects - Part B
• Reference and VOC specific NTs
• Reference and VOC specific NTs
• Reference and VOC specific NTs
• Reference and VOC specific NTs
Immunogenicity COVID-19 vaccine-naïve subjects - Part B
• Reference strain NTs
• Reference strain NTs
• Reference and VOC specific NTs
• Reference and VOC specific NTs
Safety-Part C:
• Local reactions (pain, tenderness, erythema/redness, induration/swelling)
•Systemic events (fever, fatigue, headache, chills, vomiting, nausea, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
•AEs
•SAEs
Immunogenicity - BNT162b2 experienced subjects - Part C
•VOC specific NTs
• VOC specific SRs |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please see section 1.3 for detailed timepoints of evaluation of these end points
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| E.5.2 | Secondary end point(s) |
Immunogenicity - Part A
• Reference and VOC specific NTs
BNT162b2-experienced subjects- Part B
• Reference and VOC specific NTs
• Reference and VOC specific NTs
COVID-19 vaccine-naïve subjects - Part B
• Reference and VOC specific NTs
• VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5])
• VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5])
Immunogenicity - Part C
VOC specific NTs |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please see section 1.3 for detailed timepoints of evaluation of these end points |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.2.4 | Number of treatment arms in the trial | 12 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| South Africa |
| Turkey |
| United States |
| Germany |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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