Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Individuals
- Conditions
- COVID-19SARS-CoV-2 Infection
- Registration Number
- NCT04368728
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals.
The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part.
The study will evaluate the safety, tolerability, and immunogenicity of 3 different SARS-CoV-2 RNA vaccine candidates against COVID-19 and the efficacy of 1 candidate:
* As a 2-dose (separated by 21 days) schedule;
* At various different dose levels in Phase 1;
* As a booster;
* In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age \[stratified as 12-15, 16-55 or \>55 years of age\]).
The candidate selected for efficacy evaluation in Phase 2/3 is BNT162b2 at a dose of 30 µg.
Participants who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study.
In order to describe the boostability of BNT162, and potential heterologous protection against emerging SARS-CoV-2 VOCs, an additional dose of BNT162b2 at 30 µg will be given to Phase 1 participants approximately 6 to 12 months after their second dose of BNT162b1 or BNT162b2. This will provide an early assessment of the safety of a third dose of BNT162, as well as its immunogenicity.
The assessment of boostability will be further expanded in a subset of Phase 3 participants at selected sites in the US who will receive a third dose of BNT162b2 at 30 µg or a third and potentially a fourth dose of prototype BNT162b2VOC at 30 µg (BNT162b2s01, based upon the South African variant and hereafter referred to as BNT162b2SA). A further subset of Phase 3 participants will receive a third, lower, dose of BNT162b2 at 5 or 10 µg.
To further describe potential homologous and heterologous protection against emerging SARS-CoV-2 VOCs, a new cohort of participants will be enrolled who are COVID-19 vaccine-naïve (ie, BNT162b2-naïve) and have not experienced COVID-19. They will receive BNT162b2SA given as a 2-dose series, separated by 21 days.
To reflect current and anticipated recommendations for COVID 19 vaccine boosters, participants in C4591001 who meet specified recommendations and have not already received one, will be offered a third dose of BNT162b2 after their second dose of BNT162.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47079
• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase). 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.
- Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
- Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.
- Participants who, in the judgment of the investigator, are at risk for acquiring COVID-19.
- 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.
- Capable of giving personal signed informed consent
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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.
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Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
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History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
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Receipt of medications intended to prevent COVID 19.
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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
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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
- BMI >30 kg/m2
- Anticipating the need for immunosuppressive treatment within the next 6 months
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Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
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Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
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Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
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Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
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Women who are pregnant or breastfeeding.
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Previous vaccination with any coronavirus vaccine.
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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.
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Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
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Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
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Participation in other studies involving study intervention within 28 days prior to study entry through and including 6 months 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.
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Previous participation in other studies involving study intervention containing lipid nanoparticles.
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Phase 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit.
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Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
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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.
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Phase 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention.
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Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events For 7 days after dose 1 and dose 2 Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions For 7 days after dose 1 and dose 2 Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events For 7 days after dose 1 and dose 2 Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events For 7 days after dose 1 and dose 2 Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Percentage of participants in Phase 1 reporting local reactions For 7 days after dose 1 and dose 2 Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Percentage of participants in Phase 1 reporting adverse events From dose 1 through 1 month after the last dose As elicited by investigational site staff
Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values 7 days after dose 2 As measured at the central laboratory
Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Between before dose 2 and 7 days after dose 2 As measured at the central laboratory
Percentage of participants in Phase 1 reporting serious adverse events From dose 1 through 6 months after the last dose As elicited by investigational site staff
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions For 7 days after dose 1 and dose 2 Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events From dose 1 through 1 month after the last dose As elicited by investigational site staff
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events From dose 1 through 6 months after the last dose As elicited by investigational site staff
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting serious adverse events From dose 1 through 5 or 6 months after the last dose As elicited by investigational site staff
In participants, who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting local reactions For 7 days after dose 1 (and dose 2) Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Noninferiority of the SARS-CoV-2 reference strain neutralizing titers after a third dose of BNT162b2 at 30 µg compared to after 2 doses of BNT162b2, in the same individuals 1 month after the third dose As measured at the central laboratory
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2 1 month after the second dose As measured at the central laboratory
Percentage of participants in Phase 1 reporting systemic events For 7 days after dose 1 and dose 2 Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Percentage of participants in Phase 2/3 reporting serious adverse events From dose 1 through 6 months after the last dose As elicited by investigational site staff
Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination From 7 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting adverse events From dose 1 through 1 month after the last dose As elicited by investigational site staff
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting serious adverse events From the third dose through 6 months after the third dose As elicited by investigational site staff
Percentage of participants in Phase 2/3 reporting adverse events From dose 1 through 1 month after the last dose As elicited by investigational site staff
Percentage of participants 12-15 years of age in Phase 3 reporting adverse events From dose 1 through 6 months after the last dose As elicited by investigational site staff
In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions For 7 days after dose 1 and dose 2 Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting systemic events For 7 days after the third dose Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination From 7 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting systemic events For 7 days after dose 1 (and dose 2) Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting adverse events From the third dose through 1 month after the third dose As elicited by investigational site staff
In participants who receive a third dose of BNT162b2 as a result of current or anticipated recommendations, percentage of participants reporting serious adverse events From the third dose through 6 months after the third dose As elicited by investigational site staff
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after one dose of BNT162b2SA compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals 1 month after the third dose As measured at the central laboratory
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting local reactions For 7 days after the third dose Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as a result of current or anticipated recommendations, percentage of participants reporting adverse events From the third dose through 1 month after the third dose As elicited by investigational site staff
- Secondary Outcome Measures
Name Time Method Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels Through 2 years after the final dose As measured at the central laboratory
Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels Through 2 years after the final dose As measured at the central laboratory
Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
Incidence of asymptomatic SARS CoV-2 infection 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 Through 1 month after the second dose Per 1000 person-years of follow-up
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after a third dose of BNT162b2 at 30 µg compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals 1 month after the third dose As measured at the central laboratory
In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point Through 2 years after the final dose As measured at the central laboratory
In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs Through 2 years after the final dose As measured at the central laboratory
In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels Through 2 years after the final dose As measured at the central laboratory
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
Incidence of asymptomatic SARS CoV-2 infection 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 Through 6 months after the second dose Per 1000 person-years of follow-up
Noninferiority of the SARS-CoV-2 reference strain neutralizing titers after one dose of BNT162b2SA compared to after 2 doses of BNT162b2, in the same individuals 1 month after the first dose of BNT162b2SA As measured at the central laboratory
Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination From 14 days after the second dose of study intervention to the end of the study, up to 2 years Per 1000 person-years of follow-up
GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age) 1 month after the second dose As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals 1 month after the second dose of BNT162b2SA As measured at the central laboratory
In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs Through 2 years after the final dose As measured at the central laboratory
In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point Through 2 years after the final dose As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA to after 2 doses of BNT162b2 1 month after the second dose As measured at the central laboratory
Comparison of the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2SA to after 2 doses of BNT162b2 1 month after the second dose As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 1 dose of BNT162b2SA to after a third dose of BNT162b2 at 30 µg 1 month after the first dose of BNT162b2SA/third dose of BNT162b2 As measured at the central laboratory
Trial Locations
- Locations (147)
North Alabama Research Center, LLC
🇺🇸Athens, Alabama, United States
Birmingham Clinical Research Unit
🇺🇸Birmingham, Alabama, United States
Medical Affiliated Research Center
🇺🇸Huntsville, Alabama, United States
Optimal Research, LLC
🇺🇸Huntsville, Alabama, United States
Alliance for Multispecialty Research, LLC
🇺🇸Knoxville, Tennessee, United States
Chinle Comprehensive Health Care Facility
🇺🇸Chinle, Arizona, United States
Johns Hopkins Center for American Indian Health
🇺🇸Shiprock, New Mexico, United States
The Pain Center of Arizona
🇺🇸Phoenix, Arizona, United States
HOPE Research Institute
🇺🇸Phoenix, Arizona, United States
Whiteriver Indian Hospital
🇺🇸Whiteriver, Arizona, United States
Scroll for more (137 remaining)North Alabama Research Center, LLC🇺🇸Athens, Alabama, United States