This was a massive, multi-stage effort to find a safe and effective COVID-19 vaccine. The study tested three different RNA vaccine candidates in nearly 47,000 healthy people. The goal was to pick the best formula and the right dose. The research unfolded in phases. First, scientists worked to identify the preferred vaccine candidate and dose. Then, they expanded the study to test how well that chosen vaccine actually worked at preventing COVID-19. The candidate selected for this large-scale efficacy test was called BNT162b2, given as two shots, 21 days apart. The study included people from age 12 up to 85, looking at how the vaccine performed in different age groups. A key part of the research was understanding 'boostability'—whether giving an extra dose months later could strengthen protection, especially against new variants of the virus. To test this, some participants received a third dose of the original vaccine or a version tweaked to target a specific variant. The study also enrolled a new group of people who had never had COVID-19 or a vaccine to test a two-dose series of that variant-targeted shot. Throughout, the study closely tracked local reactions (like pain at the injection site) and systemic events (like fever) after each dose to build a clear picture of safety.
How did the original COVID-19 vaccine hold up? A massive study tested its safety and effectiveness in nearly 47,000 people.
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What this means for you:
A large trial identified a preferred COVID-19 vaccine candidate and tested its safety, efficacy, and response to booster doses. What this means for you:
A large trial identified a preferred COVID-19 vaccine candidate and tested its safety, efficacy, and response to booster doses. View Original Abstract ↓
Status: COMPLETED | Phase: PHASE2/PHASE3
Condition(s): SARS-CoV-2 Infection, COVID-19
Intervention(s): BNT162b1 (BIOLOGICAL), BNT162b2 (BIOLOGICAL), Placebo (OTHER), BNT162b2SA (BIOLOGICAL)
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.
Primary Outcome(s): Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Phase 1; Percentage of Participants With Local Reactions Within 7 Days After Dose 2: Phase 1; Percentage of Participants With Systemic Events Within 7 Days After Dose 1: Phase 1
Enrollment: 46969 (ACTUAL)
Lead Sponsor: BioNTech SE
Start: 2020-04-29 | Primary Completion: 2023-02-10
Results posted: 2026-03-25