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Cochrane COVID-19 Study Register
Study record
NCT04368728First Published: 2020 Apr 30Updated Date: 2022 Feb 22

A Phase 1/2, Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding Study to Describe the Safety, Tolerability, Immunogenicity, and Potential Efficacy of SARS-COV-2 RNA Vaccine Candidates Against COVID-19 in Healthy Adults

  1. Study Type
  2. Interventional
  1. Study Aim
  2. Prevention
  1. Study Design
  2. Parallel/Crossover
  1. Intervention Assignment
  2. Randomised
  1. Population (8)
  2. Male and Female
  3. Healthy
  4. Adult
  5. Aged (65+)
  6. Child
  1. Intervention (2)
  2. COVID-19 vaccine
  3. Intramuscular
  1. Comparison (2)
  2. Placebo
  3. Intramuscular
  1. Outcome (6)
  2. COVID-19
  3. Blood Count
  4. Local Reaction
  5. Adverse Event
  6. Neutralizing antibody
  7. Blood chemistry measurement
Reference record

RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study (preprint)

Walsh EE, Frenck R, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi P-Y, Tureci O, Thompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Sahin U, Gruber WC
Unpublished article (preprint)
Report Results
Background: Severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) infections and the resulting disease, coronavirus disease 2019 (COVID−19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available. Methods: Healthy adults 18−55 and 65−85 years of age were randomized in an ongoing, placebo−controlled, observer−blinded dose−escalation study to receive 2 doses at 21−day intervals of placebo or either of 2 lipid nanoparticle−formulated, nucleoside−modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS−CoV−2 receptor-binding domain, or BNT162b2, which encodes a prefusion stabilized membrane-anchored SARS−CoV−2 full-length spike. In each of 13 groups of 15 participants, 12 received vaccine and 3 received placebo. Groups were distinguished by vaccine candidate, age of participant, and vaccine dose level. Interim safety and immunogenicity data of BNT162b1 in younger adults have been reported previously from US and German trials. We now present additional safety and immunogenicity data from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation. Results: In both younger and older adults, the 2 vaccine candidates elicited similar dose-dependent SARS−CoV−2−neutralizing geometric mean titers (GMTs), comparable to or higher than the GMT of a panel of SARS−CoV−2 convalescent sera. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults. Conclusion: These results support selection of the BNT162b2 vaccine candidate for Phase 2/3 large−scale safety and efficacy evaluation, currently underway.Competing Interest StatementCompeting interests: NK, JA, AG, SL, RB, KAS, PL, KK, WK, DC, KRT, PRD, WCG, and KUJ are employees of Pfizer and may hold stock options. US and OT are stock owners, management board members, and employees at BioNTech SE (Mainz, Germany) and are inventors on patents and patent applications related to RNA technology. MJM, KEL, KN, EEW, ARF, RF, and VR received compensation from Pfizer for their role as study investigators. CFG and PYS received compensation from Pfizer to perform the neutralization assay.Clinical TrialNCT04368728Funding StatementBioNTech is the sponsor of the study. Pfizer was responsible for the design, data collection, data analysis, data interpretation, and writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit the data for publication. All study data were available to all authors.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was approved by the institutional review boards for each participating site prior to enrollment of any study participant in this studyAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesUpon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also pro ide access to the related individual anonymized participant data.https://www.pfizer.com/science/clinical-trials/trial-data-and-results [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

The BNT162b2 (BioNTech/Pfizer) vaccine had 95% efficacy against COVID-19 ≥7 days after the 2nd dose

Chagla Z
Journal article
Report Results
SOURCE CITATION: Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603-15. 33301246
Reference record

Pfizer and BioNTech Announce Vaccine Candidate Against COVID-19 Achieved Success in First Interim Analysis from Phase 3 Study

BioNTech, Pfizer
Trial registry record
Report Results
Vaccine candidate was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis Analysis evaluated 94 confirmed cases of COVID-19 in trial participants Study enrolled 43,538 participants, with 42% having diverse backgrounds, and no serious safety concerns have been observed; Safety and additional efficacy data continue to be collected Submission for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) planned for soon after the required safety milestone is achieved, which is currently expected to occur in the third week of November Clinical trial to continue through to final analysis at 164 confirmed cases in order to collect further data and characterize the vaccine candidate’s performance against other study endpoints
Reference record

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC, C4591001 Clinical Trial Group
Journal article(Polack) Fundacion INFANT, Buenos Aires, Argentina (Marc) ITrials-Hospital Militar Central, Buenos Aires, Argentina (Thomas) State University of New York, Upstate Medical University, Syracuse, NY, United States (Absalon, Gurtman, Swanson, Koury, Kalina, Cooper, Dormitzer, Jansen, Gruber) Vaccine Research and Development, Pfizer, Pearl River, NY, United States (Kitchin, Lockhart, Bailey) Vaccine Research and Development, Pfizer, Hurley, United Kingdom (Perez, Li) Vaccine Research and Development, Pfizer, Collegeville, PA, United States (Mather) Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Collegeville, PA, United States (Moreira) Associacao Obras Sociais Irma Dulce and Oswaldo Cruz Foundation, Bahia, Brazil (Zerbini) Centro Paulista de Investigacao Clinica, Sao Paulo, Brazil (Roychoudhury) Global Product Development, Pfizer, Peapack, NJ, United States (Frenck) Cincinnati Children's Hospital, Cincinnati, United States (Hammitt) Johns Hopkins Bloomberg School of Public Health, Baltimore, United States (Tureci, Sahin) BioNTech, Mainz, Germany (Schaefer) Medizentrum Essen Borbeck, Essen, Germany (Nell) Tiervlei Trial Centre, Karl Bremer Hospital, Cape Town, South Africa (Unal) Hacettepe University, Ankara, Turkey (Tresnan) Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Groton, CT, United States
Report Results
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. METHODS: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. RESULTS: A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
Reference record

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates (preprint)

Vogel A, Kanevsky I, Che Y, Swanson K, Muik A, Vormehr M, Kranz L, Walzer K, Hein S, Gueler A, Loschko J, Maddur M, Tompkins K, Cole J, Lui BG, Ziegenhals T, Plaschke A, Eisel D, Dany S, Fesser S, Erbar S, Bates f, Schneider D, Jesionek B, Saenger B, Wallisch A-K, Feuchter Y, Junginger H, Krumm S, Heinen A, Adams-Quack P, Schlereth J, Kroener C, Hall-Ursone S, Brasky K, Griffor MC, Han S, Lees J, Mashalidis E, Sahasrabudhe P, Tan C, Pavliakova D, Singh G, Fontes-Garfias C, Pride M, Scully I, Ciolino t, Obregon J, Gazi M, Carrion R, Alfson K, Kalina W, Kaushal D, Shi P-Y, Klamp T, Rosenbaum C, Kuhn A, Tuereci O, Dormitzer P, Jansen K, Sahin U
Unpublished article (preprint)
Report Results
To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD up, two-RBD down state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNy+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728).Competing Interest StatementU.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.He., A.G., T.Z., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., A.P.H., P.A., J.S., C.K., and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.He., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A., J.S., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S., J.L., M.M., K.T., M.C.G., S.H., J.A.L.,E.H.M., P.V.S., C.Y.T., D.P., G.S., M.P., I.L.S., T.C., J.O., W.V.K., P.R.D. and K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; J.C., S.H.-U, K.B., R.C., jr., K.J.A. and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; no other relationships or activities that could appear to have influenced the submitted work. [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy IndividualsVaccine Candidates Against COVID-19 in Healthy Adults

NCT04368728
Trial registry record
No Results
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 2 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; 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 evaluation in Phase 2/3 is BNT162b2 (mid-dose). The study consists of 3 stages. Stage 1: to identify preferred vaccine candidate(s), dose level(s), number of doses, and schedule of administration (with the first 15 participants at each dose level of each vaccine candidate comprising a sentinel cohort); Stage 2: an expanded-cohort stage; and Stage 3; a final candidate/dose large-scale stage
Reference record

Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: interim Report

Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart SP, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fonter-Garfias C, Shi P-Y, Tuereci O, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Sahin U, Jansen KU
Unpublished article (preprint)
Report Results
In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 μg, 30 μg, or 100 μg of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.Competing Interest StatementCompeting interests NK, JA, AG, SL, RB, KS, PL, KK, WK, DC, KT, PRD, WG, and KUJ are employees of Pfizer and may hold stock options. US and OT are stock owners, management board members, and employees at BioNTech SE (Mainz, Germany) and are inventors on patents and patent applications related to RNA technology. MJM, KL, KN, EW, AF, RF, and VR received compensation from Pfizer for their role as study investigators. CFG and PYS received compensation from Pfizer to perform the neutralization assay. Clinical TrialClinicalTrials.gov identifier: NCT04368728 Funding StatementRole of the funding source: BioNTech is the Sponsor of the study. Pfizer was responsible for the design, data collection, data analysis, data interpretation, and writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit the data for publication. All study data were available to all authors.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The final protocol and informed consent document were approved by institutional review boards for each of the participating investigational centers This study was conducted in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and the ethical principles of the Declaration of Helsinki. A signed and dated informed consent form was required before any study-specific activity was performed. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesUpon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual anonymized participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults

Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Tureci O, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Sahin U, Jansen KU
Journal article
Report Results
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate
Reference record

Reanalysis of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine data fails to find any increased efficacy following the boost: implications for vaccination policy and our understanding of the mode of action (preprint)

Saul A, Drummer HE, Scott N, Spelman T, Crabb BS, Hellard M
Unpublished article (preprint)
Report Results
Background In clinical trials two vaccinations with mRNA vaccines have shown high efficacy in preventing COVID-19. However, in the context of a pandemic, the time to generation of protective immunity, the need for and timing of a second vaccination are matters of legitimate debate. This manuscript explores the efficacy and timing of the second dose COVID-19 vaccines, including a reanalysis of data from the Pfizer mRNA BNT162b2 mRNA SARS-CoV-2 vaccine phase 3 study. Methods and findings A non-weighted three-segment, two knot linear regression was fitted to the published cumulative infection incidence from the Pfizer BNT162b2 vaccine Phase III trial using the lspine routine in R. The optimal knot days were estimated through sensitivity analysis and the confidence limits for efficacy estimates were determined by Monte Carlo Simulations. This analysis showed the vaccine was effective from day 11 post first vaccination. The estimated efficacy over the period 11 to 28 days post first vaccination was 0.94 and there was no detectable increase in efficacy following the second vaccination. The efficacy post first vaccination substantially preceded the development of detectable serum neutralizing antibody. Conclusions Strongly protective immunity develops rapidly following a single vaccination and at least in the short period covered by the timetable of the Phase III trial, there was no additional benefit from a second vaccination. This increases options for use of this vaccine, e.g., for ring fence vaccination, for use in travelers and for mass vaccination rollout. It highlights the need for further research into duration of immunity following a single vaccination and for understanding mechanisms of protection.Competing Interest StatementNS and MH provide guidance to the Victorian Government COVID-19 response and receive funding from the Victorian Government for the Optimise Study and COVID-19 modelling work. NS received funding from Johnson & Johnson in Jun-Sep 2020 to provide incidence projections for potential vaccine trial sites. BC serves on the Australian National COVID-19 Health Research Advisory Committee that provides guidance to the Australian Federal Government COVID-19 response. Clinical Trialre-analysis of published data from NCT04368728Funding StatementNo external fundingAuthor DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:No IRB/oversight is required. Re-analysis of published data.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesPrimary data is available from publications listed in the paper. Data derived from these publications are listed in the text and in a supplementary file [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

Thomas S J, Moreira E D, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez J L, Marc G P, Polack F P, Zerbini C, Bailey R, Swanson K A, Xu X, Roychoudhury S, Koury K, Bouguermouh S, Kalina W V, Cooper D, Frenck R W, Hammitt L L, Tureci O, Nell H, Schaefer A, Unal S, Yang Q, Liberator P, Tresnan D B, Mather S, Dormitzer P R, Sahin U, Gruber W C, Jansen K U, C4591001 Clinical Trial Group
Unpublished article (preprint)
Report Results
BackgroundBNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable. Methods: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 [≥]16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 {micro}g BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination. ResultsBNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0-93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%-100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% (95% CI 80.3-99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed. Conclusion: With up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. (ClinicalTrials.gov number, NCT04368728) [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

1558O COVID-19 vaccine in participants (ptcpts) with cancer: subgroup analysis of efficacy/safety from a global phase III randomized trial of the BNT162b2 (tozinameran) mRNA vaccine

Thomas SJ, Perez JL, Lockhart SP, Hariharan S, Kitchin N, Bailey R, Liau K, Lagkadinou E, Tureci O, Sahin U, Xu X, Dychter SS, Lu C, Gentile T, Gruber W
Journal article(Thomas) Institute for Global Health and Translational Sciences, State University of New York, Upstate Medical University, Syracuse, NY, United States (Perez) Vaccine Research and Development, Pfizer, Collegeville, PA, United States (Lockhart, Kitchin, Bailey) Vaccine Research and Development, Pfizer, Maidenhead, United Kingdom (Hariharan) Oncology, Pfizer, New York, NY, United States (Liau) Pfizer, La Jolla, CA, United States (Lagkadinou) Clinical Research, Clinical Development, BioNTech SE, Mainz, Germany (Tureci, Sahin) BioNTech SE, Mainz, Germany (Xu) Biostatistics, Pfizer, Collegeville, PA, United States (Dychter) Global Product Development, Pfizer, San Diego, CA, United States (Lu, Gruber) Vaccine Research and Development, Pfizer, Pearl River, NY, United States (Gentile) State University of New York, Upstate Medical University, Syracuse, NY, United States
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Background: Patients with cancer are at higher risk of developing COVID-19 disease, adverse outcomes, and increased mortality. Phase III COVID-19 vaccine trials have demonstrated safety/efficacy against COVID-19 and prevented hospitalizations and deaths; however, most excluded ptcpts with cancer. We present phase 3 tozinameran mRNA COVID-19 vaccine trial results from ptcpts with a cancer history at baseline, either ongoing or not, per the Charlson Comorbidity Index and up to 6 months of follow-up. Method(s): Between Jul 2020-Jan 2021, 46429 ptcpts >=12 y at 152 sites in 6 countries were randomized in a placebo-controlled, observer-blinded trial of 2-dose tozinameran, showing 95% protection against COVID-19 and favorable safety (Polack et al NEJM, Dec 2020). After emergency use authorization, ptcpts were allowed to unblind and placebo recipients received vaccine. Data prior to unblinding for crossover up to 13 Mar 2021 are presented for ptcpts >=16 y for safety and >=12 y for efficacy. Adverse event (AE) data are controlled for follow-up time before unblinding and reported as incidence rate (IR) per 100-person-y of follow-up. Result(s): Of ptcpts >=16 y, 1647 had a prior diagnosis of cancer and were not on active immunosuppressive treatment (755 M; 892 F; median age 66 y [range 22-91]). Most common solid cancers included breast (n=458), prostate (n=360), and melanoma (n=210). AEs were reported at IRs of 94.0 (vaccine) and 49.3 (placebo) per 100-person-y; most common AEs were reactogenicity events (injection-site pain [IR: 40.2 vaccine; 4.2 placebo]; fatigue [IR: 21.4 vaccine; 7.6 placebo]; pyrexia [IR: 19.8 vaccine; 0.7 placebo]). 1 vaccine ptcpt withdrew due to a vaccine-related AE. No vaccine-related deaths were reported. Among ptcpts >=12 y with cancer, 3 vaccine and 27 placebo recipients developed COVID-19 from 7 days post-Dose 2; vaccine efficacy (VE) was 89.7% (95% CI 66.5-98.0%). This compares favorably with overall VE of 91.1%. Updated results will be presented. Conclusion(s): Tozinameran has similar efficacy/safety in ptcpts with cancer as in the overall population. These results inform tozinameran use in COVID-19 and in future trials in patients with cancer. Clinical trial identification: NCT04368728. Editorial acknowledgement: Editorial assistance was provided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer. Legal entity responsible for the study: Study sponsored by BioNTech, managed by Pfizer. Funding(s): Pfizer and BioNTech. Disclosure: S.J. Thomas: Financial Interests, Personal and Institutional, Research Grant, Advisory role: Pfizer. J.L. Perez: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.P. Lockhart: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S. Hariharan: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. N. Kitchin: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. R. Bailey: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. K. Liau: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. E. Lagkadinou: Financial Interests, Personal, Full or part-time Employment: BioNTech. O. Tureci: Financial Interests, Personal, Research Grant: BioNTech. U. Sahin: Financial Interests, Personal, Research Grant: BioNTech. X. Xu: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.S. Dychter: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. C. Lu: Financial Interests, Personal, Full or part-time Employment: Pfizer. W. Gruber: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. All other authors have declared no conflicts of interest.Copyright © 2021 European Society for Medical Oncology
Copyright 2021 Elsevier B.V., All rights reserved
Reference record

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months

Thomas SJ, Moreira ED, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Polack FP, Zerbini C, Bailey R, Swanson KA, Xu X, Roychoudhury S, Koury K, Bouguermouh S, Kalina WV, Cooper D, Frenck RW, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Yang Q, Liberator P, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Gruber WC, Jansen KU, C4591001 Clinical Trial Group
Journal article
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BACKGROUND: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable. METHODS: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination. RESULTS: BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed. CONCLUSIONS: Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
Reference record

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Walsh EE, Frenck RW, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Tureci O, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Sahin U, Gruber WC
Journal article(Walsh, Frenck, Falsey, Kitchin, Absalon, Gurtman, Lockhart, Neuzil, Mulligan, Bailey, Swanson, Li, Koury, Kalina, Cooper, Fontes-Garfias, Shi, Tureci, Tompkins, Lyke, Raabe, Dormitzer, Jansen, Sahin, Gruber) From the University of Rochester and Rochester General Hospital, Rochester (E.E.W., A.R.F.), Vaccine Research and Development, Pfizer, Pearl River (J.A., A.G., K.A.S., K.K., W.K., D.C., K.R.T., P.R.D., K.U.J., W.C.G.), and New York University Langone Vaccine Center and Grossman School of Medicine, New York (M.J.M., V.R.) - all in New York; Cincinnati Children's Hospital, Cincinnati (R.W.F.); Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); the University of Maryland School of Medicine, Center for Vaccine Development and Global Health, Baltimore (K.N., K.E.L.); Vaccine Research and Development, Pfizer, Collegeville, PA (P.L.); the University of Texas Medical Branch, Galveston (C.F.-G., P.-Y.S.); and BioNTech, Mainz, Germany (OT., U.S.)
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. METHODS: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. RESULTS: A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. CONCLUSIONS: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
Reference record

Efficacy and safety of the BNT162b2 mRNA COVID-19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial

Thomas SJ, Perez JL, Lockhart SP, Hariharan S, Kitchin N, Bailey R, Liau K, Lagkadinou E, Tureci O, Sahin U, Xu X, Koury K, Dychter SS, Lu C, Gentile TC, Gruber WC
Journal article
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INTRODUCTION: Individuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months' follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine. PATIENTS AND METHODS: Between July 2020-January 2021, 46,429 participants aged ≥ 12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥ 16 years for safety and ≥ 12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up. RESULTS: At baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months' follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4(BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported. CONCLUSION: In participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer. Clinical trial number: NCT04368728