Impfstoff Johnson &Amp; Johnson Lieferung

List des authors.Jerald Sadoff, M.D., Glenda Gray, M.B., B.Ch., an Vandebosch, Ph.D., Vicky Cárdenas, Ph.D., Georgi Shukarev, M.D., Beatriz Grinsztejn, M.D., paul A. Goepfert, M.D., Carla Truyers, Ph.D., Hein Fennema, Ph.D., Bart Spiessens, Ph.D., metall Offergeld, M.Sc., Gert Scheper, Ph.D., kimberly L. Taylor, Ph.D., Merlin L. Robb, M.D., john Treanor, M.D., Dan H. Barouch, M.D., Jeffrey Stoddard, M.D., martin F. Ryser, M.D., mar A. Marovich, M.D., catalen M. Neuzil, M.D., Lawrence Corey, M.D., nancy Cauwenberghs, Ph.D., Tamzin Tanner, Ph.D., karin Hardt, Ph.D., havier Ruiz-Guiñazú, M.D., Mathieu Le Gars, Ph.D., Hanneke Schuitemaker, Ph.D., Johan ventil Hoof, M.D., frank Struyf, M.D., and Macaya Douoguih, M.D.et al.,

ns members von the ENSEMBLE Study kopieren, gruppe are listed in the Supplementary Appendix, available hinweisen miyvue.com.

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Abstract

Background

The Ad26.COV2.S vaccine zu sein a recombinant, replication-incompetent human adenovirus form 26 vector encoding full-length significant acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation.

Methods

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Download a PDF des the research Summary.

In bei international, randomized, double-blind, placebo-controlled, bühne 3 trial, we randomly assigned adult participants bei a 1:1 ratio zu receive a single dose des Ad26.COV2.S (5×1010 famous particles) or placebo. Ns primary ende points were vaccine efficacy against moderate zu severe–critical coronavirus disease 2019 (Covid-19) with in onset weist least 14 days und at the very least 28 work after management among participants in the per-protocol population who had actually tested negative for SARS-CoV-2. Safety and security was so assessed.

Results

The per-protocol population included 19,630 SARS-CoV-2–negative attendees who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected versus moderate to severe–critical covid-19 with onset at least 14 days after administration (116 cases bei the vaccine gruppe vs. 348 in the placebo group; efficacy, 66.9%; readjusted 95% trust interval , 59.0 kommen sie 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 zu 74.8). Vaccine efficacy was higher against severe–critical covid-19 (76.7% for onset punkt ≥14 days und 85.4% for onset punkt ≥28 days). Regardless of 86 von 91 situations (94.5%) an South Africa through sequenced viruist having ns 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% versus moderate kommen sie severe–critical covid19 with onset weist least 14 days und at the very least 28 days after administration, respectively, und efficacy versus severe–critical covid19 was 73.1% und 81.7%, respectively. Reactogenicity was higher v Ad26.COV2.S than through placebo but was generally mild zu moderate and transient. Die incidence des serious adverse events was balanced bolzen the 2 groups. 3 deaths occurred bei the vaccine kopieren, gruppe (none were Covid-19–related), und 16 an the placebo kopieren, gruppe (5 to be Covid-19–related).

Conclusions

A einzel dose of Ad26.COV2.S protected against symptomatic Covid-19 und asymptomatic SARS-CoV-2 infection und was effective against severe–critical disease, including hospitalization and death. Safety and security appeared kommen sie be similar kommen sie that bei other phase 3 trials of covid19 vaccines. (Funded von Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.)

Introduction


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QUICK TAKESingle-Dose Ad26.COV2.S Vaccine versus Covid-19 02:17

Since emerging in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity und mortality, with new variants swiftly spreading.1-4 Vaccines kommen sie prevent covid disease 2019 (Covid-19) schutz been occurred with unmatched speed.5,6

The Ad26.COV2.S vaccine comprises a recombinant, replication-incompetent person adenovirus form 26 (Ad26) vector7 encoding a full-length, membrane-bound SARS-CoV-2 spike protein bei a prefusion-stabilized conformation.8,9 various other Ad26-based vaccines, including bei approved Ebola vaccine, are safe und have induced long lasting immune responses.8,10-13 Ad26.COV2.S induced resilient protection hinweisen low doses bei preclinical SARS-CoV-2 challenge studies,8,14 und initial clinical charme showed the a single dose weist 5×1010 famous particles was safe und induced terrific humoral und cellular immune responses.9 Ad26.COV2.S can be stored for up to 2 years an a standard freezer and up kommen sie 3 months punkt refrigerator temperatures, i m sorry simplifies transport, storage, und use bei a pandemic.

We space conducting bei ongoing bühne 3 attempt (ENSEMBLE) kommen sie evaluate die safety and efficacy von a single dose des Ad26.COV2.S hinweisen 5×1010 viral particles zum the prevention von Covid-19 and SARS-CoV-2 infection in adults. Here, us report ns results von the major analyses.


Trial Design and Oversight

We space conducting this ongoing, 2-year, multicenter, randomized, double-blind, placebo-controlled, bühne 3, pivotal trial in Argentina, Brazil, Chile, Colombia, Mexico, Peru, southern Africa, and the united States. All ns participants provided written educated consent. Ns trial adheres to die principles von the Declaration des Helsinki und to the Good Clinical exercise guidelines von the international Council for Harmonisation. The protocol (available with ns full text of this article hinweisen miyvue.com) und amendments were approved by institutional evaluation boards according to local regulations. In unblinded independent data und safety surveillance board repetitively monitors safety, consisting of monitoring zum vaccine-associated magnified respiratory disease.

The trial is a collaboration bolzen the sponsor, Janssen Research and Development, i m sorry is in affiliate von Janssen Vaccines und Prevention und part of the Janssen pharmaceutical service providers of johnson & Johnson, und the procedure Warp Speed covid19 Rapid Response mannschaft (which includes the Biomedical advanced Research und Development Authority, the national Institutes of Health, the covid-19 Prevention Trials Network, and the Department of Defense). The trial was designed und conducted, and the dünn analysis and data translate were performed, über the sponsor and collaborators. Trial-site investigators collected and contributed to ns interpretation des the data. Every the säule were easily accessible to the authors, who vouch weil das the accuracy and completeness von the data und for the fidelity von the attempt to the protocol. Medical writers who were funded von the sponsor assisted an drafting the manuscript.

Trial Participants

Stages 1a und 2a von the trial were conducted in parallel und included 2000 adult 18 zu 59 years of age und 60 years of age or older, respectively, that were in good or secure health and did not schutz coexisting conditions that schutz been damit verbundenen with an increased risk von severe Covid-19. After a 3-day security review von the data und safety surveillance board, stages 1b and 2b to be initiated. Those stages additionally included adults von the exact same respective period ranges who had actually stable und well-controlled coexisting conditions. Die eligibility criteria space provided an the Supplementary methods section in the Supplementary Appendix, available at miyvue.com. Entrants were notfall excluded on the basis of SARS-CoV-2 epidemic or serostatus.

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Procedures

Details von the trial steps are provided bei the Supplementary approaches section. Participants were randomly assigned in a 1:1 ratio, with ns use of randomly permuted blocks, to receive either Ad26.COV2.S or saline placebo. Randomization was conducted with bei interactive Web-response system und stratified according zu trial site, age group, and the existence or absence von coexisting conditions that schutz been relevant with bei increased risk von severe Covid-19.

Vaccine or placebo was administered on day 1. Ad26.COV2.S was supplied bei single-use vials at a concentration des 1×1011 famous particles per milliliter und was administered weist a dose von 5×1010 viral particles as a single intramuscular injection (0.5 ml) by a health care worker who was unaware von the gruppe assignment.

Participants reported covid19 symptoms electronically using the Symptoms of Infection v Coronavirus-19 questionnaire (methods described an Fig. S1 in the Supplementary Appendix). Participants and trial staff acquired nasal swabs, which to be tested with die use des a Food und Drug administration (FDA) emergency Use Authorization reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay for SARS-CoV-2 at a regional laboratory und subsequently shown centrally (m-2000 SARS-CoV-2 real-time RT-PCR, Abbott). Seropositivity for SARS-CoV-2 was evaluated von means des a SARS-CoV-2 nucleocapsid (N) immunoassay (Elecsys, Roche) weist trial entry and on work 29 und 71. Assays were performed according to ns manufacturers’ protocols.

Primary and key an additional efficacy evaluations were based upon centrally evidenced cases von Covid-19. Owing to die high incidence des Covid-19 und the time taken zum central confirmation, not all situations had been centrally evidenced at die time von the main analysis. A supplementary analysis von RT-PCR–positive situations from every sources, whether centrally shown or not, was therefore performed zum subgroups, hospitalizations, und deaths.

Safety Assessments

Serious disadvantage events and adverse occasions leading zu withdrawal from the trial are being videotaped throughout die trial. An a safety subpopulation comprising about 6000 entrants (see below), data on solicited local und systemic adverse events were tape-recorded in in electronic diary zum 7 work after administration and unsolicited disadvantage events zum 28 work after administration.

Efficacy Assessments

The 2 primary ende points were ns efficacy von the Ad26.COV2.S vaccine against the first occurrence des centrally evidenced moderate zu severe–critical covid19 with bei onset punkt least 14 work after administration und at least 28 days after administration in the per-protocol population (see below). All the potential cases des severe–critical Covid-19 und cases des moderate covid19 with punkt least three indications or symptoms to be classified as being severe–critical by bei independent Clinical Severity Adjudication Committee whose members were unaware of the group assignments. This committee adjudicated instances on the basis of clinical referee (e.g., a einzel low oxygen-saturation measure up was not classified together indicating severe covid-19 unless various other clinical result were constant with a significant classification). Ns case definitions zum Covid-19 und the protocol-defined secondary und exploratory end points space described an the Supplementary Appendix.

Statistical Analysis

The full analysis set included all ns participants that underwent randomization and received a dose of trial vaccine or placebo. The per-protocol population comprised attendees who got a dose des trial vaccine or placebo, were seronegative or had an unknown serostatus at the time that ns vaccine or placebo was administered, und had no protocol deviations that were likely zu affect vaccine efficacy. Participants that were RT-PCR–positive betwee days 1 and 14 or betwee days 1 und 28 to be excluded from ns analysis von cases with in onset hinweisen least 14 days after administration and at the very least 28 days after administration, respectively. Die per-protocol population was the main population for ns efficacy analyses. Security analyses were conducted an the full analysis set, including ns safety subpopulation.

The null hypothesis was that die efficacy von Ad26.COV2.S would be no higher than 30% weil das each primary ende point, together evaluated through a truncated sequential probability ratio test15,16 punkt a one-sided meaning level des 0.025. Die sample size was reduced native 60,000 kommen sie approximately 40,000 top top the base of ns high incidence of covid19 during ns trial. The primary analysis was triggered top top a confident recommendation from die data and safety monitoring board, after the FDA-specified typical 8-week follow-up was reached and prespecified säule requirements to be met.

If the null hypothesis was rejected zum both primary end points, secondary objectives were evaluated versus a null hypothesis that offered a reduced limit of vaccine efficacy des more 보다 0% v prespecified multiplicity adjustments for familywise type ich error manage (Fig. S2). Precise Poisson regression17 was used for the analysis of vaccine efficacy and the associated confidence expression calculations, through accounting weil das follow-up time. The cumulative incidence over time was estimated with the use des Kaplan–Meier methods kommen sie evaluate the onset of vaccine efficacy und vaccine efficacy end time. Participants had their säule censored weist the end of your follow-up.

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The frequency of serious adverse events was tabulated bei the full evaluation set. Ns frequency and severity des solicited and unsolicited adverse events were tabulated in the security subpopulation.