Trial NCT04368728
Publication Polack F, N Engl J Med, 2020
Dates: 27/07/2020 to 14/11/2020
Funding: Private (BioNTech and Pfizer)
Conflict of interest: Yes
Methods | |
RCT | |
Location :
Multicenter / Argentina, Brazil, Germany, South Africa, Turkey, USA Follow-up duration (months): 2.43 | |
• 30 mcg BNT162b2 (n = 21720) • Placebo (n = 21728) |
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Inclusion criteria | Male or female participants aged 16-85 years ; 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 ; Capable of giving personal signed informed consent |
Exclusion criteria | 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 ; History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) ; Receipt of medications intended to prevent COVID 19 ; 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 ; Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel) ; Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination ; Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection ; Women who are pregnant or breastfeeding ; Previous vaccination with any coronavirus vaccine ; ndividuals 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 ; Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study ; Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation ; Previous participation in other studies involving study intervention containing lipid nanoparticles ; 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. |
Interventions | |
Intervention
2 IM doses of 30-mcg BNT162b1 per dose on days 1, 21 |
|
Control
2 IM doses of 0.5 mL normal saline per dose on days 1 and 21 | |
Participants | |
Randomized 43548 participants | |
Characteristics of participants Type of participants: Healthy volunteers N=43548 19075 males Pregnant women: 0 Mean age: Age range: 16-89 | |
Description of participants Healthy SARS-CoV-2 DNA negative adults in multiple centres in Argentina, Brazil, Germany, South Africa, Turkey, and the USA | |
Primary outcome | |
In the register Percentage of participants in Phase 2/3 reporting adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]; Percentage of participants in Phase 2/3 reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]; Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ] ; Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ] | |
In the report Safety: The primary end points of this trial were solicited, specific local or systemic adverse events and use of antipyretic or pain medication within 7 days after the receipt of each dose … and unsolicited adverse events … through 1 month after the second dose and unsolicited serious adverse events through 6 months after the second dose. Efficacy: The first primary end point was the efficacy of BNT162b2 against confirmed Covid-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose. | |
Variants description | |
Variants | |
Description | |
Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, Upon request, and subject to review |
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
General comment |
In addition to the published paper, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. The reported results are from Phase 3 of a Phase 1/2/3 ongoing trial (NCT04368728). There were few differences between the published article and the trial registry in population, procedures, interventions and outcomes. We extracted the n randomized to be the number of randomized participants injected with vaccine or placebo after exclusions of 99 participants who underwent randomization but were not vaccinated and 1 participant who did not sign the informed consent document, as well well as 13 participants who underwent randomization after the cutoff. 37,086 participants were randomized for efficacy with a median follow up of 2 months but only 36,523 were analyzed and the reason for exclusions were unclear. Safety outcomes were assessed on the population who received 1 dose irrespective of follow up time (up to 14 weeks). Safety monitoring will continue for 2 years after administration of the second dose of vaccine. |