| E.1 Medical condition or disease under investigation |
| E.1.1 |
Medical condition(s) being investigated |
| Protection against COVID-19 |
|
| E.1.1.1 |
Medical condition in easily understood language |
| Healthy volunteers and immunocompromised subjects (prevention of infection with the Corona virus) |
|
| 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 |
|
| 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 |
| To describe the safety and tolerability profiles of prophylactic BNT162 vaccines in healthy adults after single dose (SD; prime only) or prime/boost (P/B) immunization |
|
| E.2.2 |
Secondary objectives of the trial |
| To describe the immune response in healthy adults after SD or P/B immunization measured by a functional antibody titer, e.g., virus neutralization test or an equivalent assay available by the time of trial conduct. |
|
| 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. They must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (e.g., to practice social distancing and to follow good practices to reduce their chances of being infected or spreading COVID-19), and other requirements of the trial.
3. They must be able to understand and follow trial-related instructions.
4. For younger subject cohorts, volunteers must be aged 18 to 55 years, have a BMI over 19 kg/m2 and under 30 kg/m2, and weigh at least 50 kg at Visit 0.
OR
For older adult cohorts, volunteers must be aged 56 to 85 years, have a BMI over 19 kg/m2 and under 30 kg/m2, and weigh at least 50 kg at Visit 0.
OR
For the immunocompromised adult cohort (Cohort 13), volunteers must be aged 18 to 85 years, have a BMI over 19 kg/m2 and under 30 kg/m2, and weigh at least 50 kg at Visit 0.
5. They must be healthy, in the clinical judgment of the investigator, based on medical history, physical examination, 12-lead ECG, vital signs (systolic/diastolic blood pressure, pulse rate, body temperature, respiratory rate), and clinical laboratory tests (blood chemistry, hematology, and urine chemistry) at Visit 0.
Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 wks before enrollment, can be included.
OR
For the immunocompromised cohort (Cohort 13); volunteers who have previously received solid organ transplant, or peripheral blood stem cell transplantation ≥6 months after transplantation, or individuals with HIV infection with a CD4+ T-cell count of ≥200 x 106 /L at Visit 0. Individuals with lower T-cell counts will be excluded from the trial on the basis that this represents a significant medical complication. In the clinical judgment of the investigator, volunteers must be immunocompromised but otherwise healthy. After consultation with the Medical Monitor, this may include individuals receiving immunosuppressant therapy due to another confounding disease at least 2 wks prior to enrollment and/or at least 6 wks following immunization with BNT162b2, and/or individuals with immunosuppressive treatment of an autoimmune disease if the disease is stable.
6. WOCBP must have a negative beta-human chorionic gonadotropin urine test at Visit 0 and Visit 1. Women that are postmenopausal or permanently sterilized will be considered as not having reproductive potential.
7. WOCBP must agree to practice a highly effective form of contraception during the trial, starting after Visit 0 and continuously until 60 d after receiving the last immunization. WOCBP must agree to require their male partners to use condoms during sexual contact (unless male partners are sterilized or infertile).
8. WOCBP must confirm that they practiced at least one highly effective form of contraception for the 14 d prior to Visit 0.
9. WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting after Visit 0 and continuously until 60 d after receiving the last immunization.
10. Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a highly effective form of contraception with their female partner of childbearing potential during the trial, starting after Visit 0 and continuously until 60 d after receiving the last immunization.
11. Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 60 d after receiving the last immunization.
12. They must have confirmation of their health insurance coverage prior to Visit 0.
13. They must agree to not be vaccinated during the trial, starting after Visit 0 and continuously until 28 d after receiving the last immunization. |
|
| E.4 |
Principal exclusion criteria |
Volunteers are excluded from the trial if they meet or present any of the following criteria:
1. Have had any acute illness, as determined by the investigator, with or without fever, within 72 h prior to the first immunization. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the investigator, the residual symptoms will not compromise their wellbeing if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
2. Are breastfeeding on the day of Visit 0 or who plan to breastfeed during the trial, starting after Visit 0 and continuously until at least 90 d after receiving the last immunization.
3. Have a known allergy, hypersensitivity, or intolerance to the planned IMP including any excipients of the IMP.
4. Had any medical condition or any major surgery (e.g., requiring general anesthesia) within the past 5 years which, in the opinion of the investigator, could compromise their wellbeing if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments. See the inclusion criteria 5 for non-excluded medical conditions for Cohort 13.
5. Have any surgery planned during the trial, starting after Visit 0 and continuously until at least 90 d after receiving the last immunization.
6. Had any chronic use (more than 21 continuous days) of any systemic medications, including immunosuppressants or other immune-modifying drugs (except for Cohort 13), within the 6 months prior to Visit 0 unless in the opinion of the investigator, the medication would not prevent, limit, or confound the protocol-specified assessments or could compromise subject safety. Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 wks before enrollment, can be included.
7. Received any vaccination within the 28 d prior to Visit 0.
8. Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Visit 0.
9. Had administration of another investigational medicinal product including vaccines within 60 d or 5 half-lives (whichever is longer), prior to Visit 0.
10. Have a known history of active or ongoing hepatitis B or hepatitis C infection; or except for Cohort 13: HIV-1 or HIV-2 infection within the 30 d prior to Visit 0
11. Have a positive PCR-based test for SARS-CoV-2 within the 30 d prior to Visit 1.
12. Have a positive drugs of abuse (for amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, and tricyclic antidepressants) result at Visit 0 or Visit 1.
13. Have a positive breath alcohol test at Visit 0 or Visit 1.
14. Previously participated in an investigational trial involving lipid nanoparticles.
15. Are subject to exclusion periods from other investigational trials or simultaneous participation in another clinical trial. When entering the follow-up phase, i.e., after completing the EoT visit, subjects are allowed to participate in other clinical trials not investigating COVID-19 vaccines or treatments.
16. Have any affiliation with the trial site (e.g., are close relative of the investigator or dependent person, such as an employee or student of the trial site).
17. Have a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions which, in the opinion of the investigator, could compromise their wellbeing if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
18. Have a history of hypersensitivity or serious reactions to previous vaccinations.
19. Have a history of Guillain-Barré syndrome within 6 wks following a previous vaccination.
20. Have a history of narcolepsy.
21. Have history of alcohol abuse or drug addiction within 1 year before Visit 0.
22. (Except for Cohort 13) Have a history of or suspected immunosuppressive condition, acquired or congenital, as determined by medical history and/or physical examination at Visit 0.
23. Have any abnormality or permanent body art (e.g., tattoo) that, in the opinion of the investigator, would obstruct the ability to observe local reactions at the injection site.
(truncated due to limited characters) |
|
| E.5 End points |
| E.5.1 |
Primary end point(s) |
* Solicited local reactions at the injection site (pain, tenderness, erythema/redness, induration/swelling) recorded up to 7 d after each immunization (trial days 8 and 29).
* Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) recorded up to 7 d after each immunization (trial days 8 and 29).
* The proportion of subjects with at least 1 unsolicited treatment-emergent adverse event (TEAE):
- For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B): occurring up to 21 d after the prime immunization (trial day 22) and 28 d after the boost immunization (trial day 50).
- For BNT162c2 (SD): The proportion of subjects with at least 1 unsolicited TEAE occurring up to 28 d after the immunization (trial day 29). |
|
| E.5.1.1 |
Timepoint(s) of evaluation of this end point |
| see Clinical Trial Protocol, Section 9.4.2 Primary endpoints |
|
| E.5.2 |
Secondary end point(s) |
For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B):
As compared to baseline at 7 and 21 d after primary immunization (trial days 8 and 22) and at 7, 14 b, 21, 28, 63, and 162 d after the boost immunization (trial days 29 to 184):
* Functional antibody responses (titers).
* Fold increase in functional antibody titers.
* Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline.
For BNT162c2 (SD): As compared to baseline at 7, 21, 28, 42, 84, and 183 d after the primary immunization (trial days 8 to 184): * Functional antibody responses (titers).
* Fold increase in functional antibody titers.
* Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline.
For Cohort 14 with BNT162b2
As compared to baseline at 7, 14, and 21 d after primary immunization (Trial days 8, 15, and 22) and at 7, 28, and 162 d after the boost immunization (trial days 29, 50, and 184):
* Functional antibody responses (titers).
* Fold increase in functional antibody titers.
* Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline. |
|
| E.5.2.1 |
Timepoint(s) of evaluation of this end point |
| see Clinical Trial Protocol, Section 9.4.3 Secondary endpoints |
|
| E.6 and E.7 Scope of the trial |
| E.6 |
Scope of the trial |
| E.6.1 |
Diagnosis |
No |
| E.6.2 |
Prophylaxis |
No |
| 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 |
| Tolerability and Immunogenicity |
|
| E.7 |
Trial type and phase |
| E.7.1 |
Human pharmacology (Phase I) |
Yes |
| E.7.1.1 |
First administration to humans |
Yes |
| E.7.1.2 |
Bioequivalence study |
No |
| E.7.1.3 |
Other |
Yes |
| E.7.1.3.1 |
Other trial type description |
| Phase I/II, 2-Part, Dose-Escalation Trial |
|
| 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 |
No |
| E.8.1.1 |
Randomised |
No |
| E.8.1.2 |
Open |
Yes |
| E.8.1.3 |
Single blind |
Information not present in EudraCT |
| E.8.1.4 |
Double blind |
Information not present in EudraCT |
| E.8.1.5 |
Parallel group |
Information not present in EudraCT |
| E.8.1.6 |
Cross over |
Information not present in EudraCT |
| E.8.1.7 |
Other |
Yes |
| E.8.1.7.1 |
Other trial design description |
| Part A: dose-escalation design and Part B: parallel cohorts |
|
| 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 |
No |
| E.8.2.4 |
Number of treatment arms in the trial |
4 |
| 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 |
5 |
| E.8.5 |
The trial involves multiple Member States |
No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 |
Trial being conducted both within and outside the EEA |
No |
| E.8.6.2 |
Trial being conducted completely outside of the EEA |
No |
| E.8.7 |
Trial has a data monitoring committee |
No |
| 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 |
| Last subject last visit (LSLV) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 |
In the Member State concerned years |
|
| E.8.9.1 |
In the Member State concerned months |
36 |
| E.8.9.1 |
In the Member State concerned days |
|
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