| 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 |
| 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 |
For Phase 1:
To describe the safety and tolerability profiles of prophylactic BNT162 vaccines in healthy adults after 1 or 2 doses
For Phase 2/3
Primary Efficacy:
- To evaluate the efficacy of prophylactic BNT162b2 against confirmed COVID 19 occurring from 7 days after the second dose in participants without evidence of infection before vaccination
- To evaluate the efficacy of prophylactic BNT162b2 against confirmed COVID 19 occurring from 7 days after the second dose in participants with and without evidence of infection before vaccination
Primary Safety:
- To define the safety profile of prophylactic BNT162b2 in the first 360 participants randomized (Phase 2)
- To define the safety profile of prophylactic BNT162b2 in all participants randomized in Phase 2/3
- To define the safety profile of prophylactic BNT162b2 in participants 12 to 15 years of age in Phase 3
Please refer to Protocol section 3 for a full list |
|
| E.2.2 | Secondary objectives of the trial |
Ph1
-To describe the immune responses elicited by prophylactic BNT162 vaccines in healthy adults after 1 or 2 doses
-please see the exploratory objectives in the protocol
Ph2/3
Secondary Efficacy:
-To evaluate the efficacy of prophylactic BNT162b2 against confirmed COVID 19 occurring from 14 days after the second dose in participants without evidence of infection before vaccination
- To evaluate the efficacy of prophylactic BNT162b2 against confirmed COVID 19 occurring from 14 days after the second dose in participants with and without evidence of infection before vaccination
- To evaluate the efficacy of prophylactic BNT162b2 against confirmed severe COVID-19 occurring from 7 days and from 14 days after the second dose in participants with and without evidence of infection before vaccination
Please refer to protocol section 3 for a full list |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants between the ages of 18 and 55 years, inclusive, and 65 and 85 years, inclusive (Phase 1), or ≥12 years (Phase 2/3), at randomization. For the boostability and protection-against-VOCs subset:
• Existing participants enrolled to receive a third dose of BNT162b2 at 30 µg or BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at rerandomization. •Newly enrolled participants enrolled to receive 2 doses of BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at enrollment. •Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg; male or female participants ≥18 years at rerandomization. Note that participants <18 years of age cannot be enrolled in the EU.
• Refer to Protocol-Appendix 4 for reproductive criteria for male (Protocol Section 10.4.1) and female (Protocol Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for Phase 3 participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) can be found in Section 10.8.
4. Phase 2/3 only: Participants who, in the judgment of the investigator, are at higher risk for acquiring COVID-19 (including, but not limited to, use of mass transportation, relevant demographics, and frontline essential workers).
5. Boostability and protection-against-VOCs existing participant subset only: Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the protocol-specified window.
Informed Consent:
6. Capable of giving personal signed informed consent/have parent(s)/legal guardian capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
4. Receipt of medications intended to prevent COVID 19.
5. Previous 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) diagnosis of COVID 19.
6. Phase 1 only: Individuals at high risk for severe COVID-19, including those with any of the following risk factors:
•Hypertension
•Diabetes mellitus
•Chronic pulmonary disease
•Asthma
•Current vaping or smoking
•History of chronic smoking within the prior year
•Chronic liver disease
•Stage 3 or worse chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2)
•Resident in a long-term facility
•BMI >30 kg/m2
•Anticipating the need for immunosuppressive treatment within the next 6 months
7. Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
8. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
9. Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren’s syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).
10. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
11. Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
12. Previous vaccination with any coronavirus vaccine.
13. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized (except for participants in Phase 1 – see exclusion criterion 14), intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
14. Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
15. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
Prior/Concurrent Clinical Study Experience:
16. Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non- Pfizer interventional studies for prevention of COVID 19, which are prohibited throughout study participation.
17. Previous participation in other studies involving study intervention containing lipid nanoparticles.
Diagnostic Assessments:
18. Phase 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit.
19. Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
Note: With the exception of bilirubin, participants with any stable Grade 1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator. (Note: A “stable” Grade 1 laboratory abnormality is defined as a report of Grade 1 on an initial blood sample that remains ≤ Grade 1 upon repeat testing on a second sample from the same participant.)
20. Phase 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening visit.
21. Phase 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention.
Please refer to Protocol section 5.2 for a full list of exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- For Phase 1
Local reactions (pain at the injection site, redness, and swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
Hematology and chemistry laboratory parameters detailed in Protocol Section 10.2
- For Phase 2/3
Primary Efficacy:
COVID-19 incidence per 1000 person-years of follow-up based on central laboratory or locally confirmed NAAT in participants with no serological or virological evidence (up to 7 days after receipt of the second dose) of past SARS-CoV-2 infection
COVID-19 incidence per 1000 person-years of follow-up based on central laboratory or locally confirmed NAAT
Primary Safety:
• Local reactions (pain at the injection site, redness, and swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
• In a subset of at least 6000 participants:
o Local reactions (pain at the injection site, redness, and swelling)
o Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
Primary Immunogenicity:
BNT162b2-experienced participants
- SARS-CoV-2 reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of the third dose of BNT162b2) of past SARS-CoV-2 infection
- SARS-CoV-2 SA and reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of 1 dose of BNT162b2SA) of past SARS-CoV-2 infection
BNT162b2-naïve participants
- SARS-CoV-2 SA and reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of the second dose of BNT162b2SA or BNT162b2 as appropriate) of past SARS CoV-2 infection
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Please see the clinical study protocol Section 3 |
|
| E.5.2 | Secondary end point(s) |
For phase 1-2
•SARS-CoV-2 neutralizing titers
•S1-binding IgG levels
•RBD-binding IgG levels
Exploratory:
• SARS-CoV-2 reference-strain neutralizing titers
• SARS-CoV-2 SA-variant neutralizing titers
• Full-length S-binding or S1 binding IgG levels
• Local reactions (pain at the injection site, redness, and swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
For Phase 2/ 3
Secondary Efficacy:
-COVID-19 incidence per 1000 person years of follow-up based on central laboratory or locally confirmed NAAT in participants with no serological or virological evidence (up to 14 days after receipt of the second dose) of past SARS-CoV-2 infection
-COVID-19 incidence per 1000 person years of follow-up based on central laboratory or locally confirmed NAAT
-Confirmed severe COVID-19 incidence per 1000 person-years of follow-up in participants with no serological or virological evidence (up to 7 days and up to 14 days after receipt of the second dose) of past SARS CoV-2 infection
-Confirmed severe COVID-19 incidence per 1000 person-years of follow-up
-COVID-19 incidence per 1000 person-years of follow-up based on central laboratory or locally confirmed NAAT in participants with no serological or virological evidence (up to 7 days and up to 14 days after receipt of the second dose) of past SARS-CoV-2 infection
-COVID-19 incidence per 1000 person-years of follow-up based on central laboratory or locally confirmed NAAT
-Incidence of asymptomatic SARS CoV-2 infection per 1000 person-years of follow-up based on N binding antibody seroconversion in participants with no serological or virological evidence of past SARS CoV-2 infection or confirmed COVID-19 prior to 1 month after receipt of the second dose
-Incidence of asymptomatic SARS CoV-2 infection per 1000 person-years of follow-up based on central laboratory–confirmed NAAT in participants with no serological or virological evidence (up to the start of the asymptomatic surveillance period) of past SARS-CoV-2 infection
Secondary Immunogenicity:
- SARS-CoV-2 neutralizing titers in participants with no serological or virological evidence (up to 1 month after receipt of the second dose) of past SARS-CoV-2 infection
BNT162b2-experienced participants
- SARS-CoV-2 SA and reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of the third dose of BNT162b2) of past SARS CoV-2 infection
- SARS-CoV-2 reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of 1 dose of BNT162b2SA) of past SARS-CoV-2 infection
- SARS-CoV-2 SA NT in participants with no serological or virological evidence (up to 1 month after receipt of 1 dose of BNT162b2SA or the third dose of BNT162b2) of past SARS CoV-2 infection
- SARS-CoV-2 SA and reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of the second dose of BNT162b2SA) of past SARS CoV-2 infection
BNT162b2-naïve participants
- SARS-CoV-2 SA NTs in participants with no serological or virological evidence (up to 1 month after receipt of the second dose of BNT162b2SA or BNT162b2 as appropriate) of past SARS CoV-2 infection
- SARS-CoV-2 reference strain NTs in participants with no serological or virological evidence (up to 1 month after receipt of the second dose of BNT162b2SA or BNT162b2 as appropriate) of past SARS CoV-2 infection
Exploratory:
•COVID-19 incidence per 1000 person-years of blinded follow-up based on central laboratory or locally confirmed NAAT
•COVID-19 incidence per 1000 person-years of follow-up based on central laboratory or locally confirmed NAAT
•Incidence of asymptomatic SARS CoV-2 infection per 1000 person-years of follow-up based on N binding antibody seroconversion in participants with no serological or virological evidence of past SARS CoV-2 infection or confirmed COVID-19
•Incidence of asymptomatic SARS CoV-2 infection per 1000 person-years of follow-up based on central laboratory–confirmed NAAT in participants with no serological or virological evidence (up to the start of the asymptomatic surveillance period) of past SARS-CoV-2 infection
•Full-length S-binding or S1 -binding IgG levels
•SARS-CoV-2 neutralizing titers
•Identification of SARS-CoV-2 variant(s)
•All safety, immunogenicity, and efficacy endpoints described above
•Detection by NAAT
•SARS-CoV-2 NTs for any VOCs not already specified
•Participants to describe the immune response to a third dose of BNT162b2 or a third or fourth dose of BNT162b2SA at later time points to align with analyses and corresponding changes detailed in the statistical section.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please see the clinical study protocol Section 3 |
|
| 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 | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| A PHASE 1/2/3, OBSERVER-BLIND, DOSE-FINDING STUDY. |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 20 |
| 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 | 6 |
| 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 | 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 |
| Argentina |
| Brazil |
| South Africa |
| United States |
| Germany |
| Turkey |
|
| 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
|
| The end of the study is defined as the date of last visit of the last participant in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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