Trial NCT04368728
Publication Thomas S, N Engl J Med, 2021
Dates: 2020-07-27 to 2021-01-11
Funding: Private (BioNTech/Pfizer)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Multinational Follow-up duration (months): 6 | |
| BNT162b2 (n = 22085)
Placebo (n=22080) |
|
| Inclusion criteria |
|
| Exclusion criteria |
|
| Interventions | |
| Intervention
2 IM doses of 30 mcg, 21 days apart |
|
| Control
2 IM doses of placebo, 21 days apart | |
| Participants | |
| Randomized 44165 participants | |
| Characteristics of participants Type of participants: Children, adolescent, adults N=44165 22420 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR | |
| Description of participants Children (>=12Y yo), adolescentes and adults, with no history or SARS-CoV 2 infection at 152 sites in Argentina, Brazil, Germany, South Africa, Turkey and USA | |
| Primary outcome | |
| In the register In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions [ Time Frame: 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 systemic events [ Time Frame: 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 the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events [ Time Frame: 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 [ Time Frame: From dose 1 through 6 months after the last dose ] As elicited by investigational site staff In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions [ Time Frame: 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 [ Time Frame: 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 adverse events [ Time Frame: From dose 1 through 1 month after the last dose ] As elicited by investigational site staff Percentage of participants in Phase 2/3 reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ] As elicited by investigational site staff 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 ] Per 1000 person-years of follow-up 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 ] Per 1000 person-years of follow-up Percentage of participants 12-15 years of age in Phase 3 reporting adverse events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events [ Time Frame: 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 BNT162b2SA given as 1 or 2 doses, percentage of participants reporting adverse events [ Time Frame: From dose 1 through 1 month 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 [ Time Frame: 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 [ Time Frame: 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 BNT162b2SA given as 1 or 2 doses, percentage of participants reporting systemic events [ Time Frame: 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, percentage of participants reporting adverse events [ Time Frame: 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, percentage of participants reporting serious adverse events [ Time Frame: From the third dose through 6 months after the third dose ] As elicited by investigational site staff In participants who receive a third dose of BNT162b2, percentage of participants reporting local reactions [ Time Frame: 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, percentage of participants reporting systemic events [ Time Frame: 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. 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 [ Time Frame: 1 month after the third dose ] As measured at the central laboratory 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 [ Time Frame: 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 [ Time Frame: 1 month after the second dose ] As measured at the central laboratory | |
| In the report Safety end points included solicited, prespecified local reactions, systemic events, and antipyretic or pain medication use during the first 7 days after receipt of each vaccine or placebo dose, which were recorded in an electronic diary; unsolicited adverse events after receipt of the first dose through 1 month after the second dose; and serious adverse events after receipt of the first dose through 1 and 6 months after the second dose was received. Safety data are presented for the blinded follow-up and open-label periods. BNT162b2 efficacy against laboratory-confirmed Covid-19 with an onset of 7 days or more after the second dose was assessed and summarized descriptively in participants without serologic or virologic evidence of SARS-CoV-2 infection within 7 days after the second dose and in participants with or without evidence of previous infection. Efficacy against severe Covid-19 was also assessed. Lineages of SARS-CoV-2 detected in midturbinate specimens are reported here for Covid-19 cases that occurred 7 days or more after the second dose in South African participants without evidence of previous infection. | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes |
| 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 all available versions of the pre-print article, the study registry and protocol were used in data extraction and risk of bias assessment. There were no substantive differences between the pre-print article and the prospective registry, protocol and statistical analysis plan in population, procedures, interventions or outcomes. The paper reports a reactogenicity subset of participants (local and systemic adverse events) but n of events could not be retrieved for these outcomes.
This report is an update of results previously reported for participants aged ≥16 years in Polack F, N Engl J Med, 2020 and for participants aged 12-15 years in Frenck R, N Engl J Med, 2021. In this report, baseline characteristics and patient disposition are reported only for the population aged ≥16 years. Efficacy results regarding symptomatic COVID-19 are reported for fully vaccinated participants aged ≥12 years without evidence of prior infection, severe or critical COVID-19 is reported for participants aged ≥12 years who received at least one dose, while safety results (mortality, adverse events and serious adverse events, withdrawals due to adverse events) are reported for all participants aged ≥16 years who received at least one dose. This trial was updated on September 15th, 2021, after publication of study report. |