7 juli 2022: Bron: N Engl J Med june 2022; 386:2084-2096

Uit een fase III studie, gerandomiseerd en placebo gecontroleerd bij totaal 24.141 vrijwilligers blijkt het zogenoemde CoVLP+AS03-vaccin effectief in het voorkomen van Covid-19 veroorzaakt door verschillende varianten van het oorspronkelijke coronavirus. De onderzoekers melden een werkzaamheid variërend van mediaan 69,5% tegen symptomatische infectie tot mediaan 78,8% tegen matige tot ernstige ziekte.

Het bijzondere aan dit CoVLP+AS03-vaccin is dat het 100 procent plantaardig is opgebouwd. De gemiddelde leeftijd van de deelnemers was wel jong met 29 jaar. Daarbij bedenkend dat het overgrote deel van de mensen die erg ziek worden van het coronavirus of er aan overlijden veel ouder zijn. 

Resultaten vrij vertaald met hulp van google translate:

  • In totaal namen 24.141 vrijwilligers deel aan deze studie; de mediane leeftijd van de deelnemers was 29 jaar. Covid-19 werd bevestigd door polymerase-ketenreactie-assay bij 165 deelnemers in de intention-to-treat-populatie; alle virale monsters waarvan de sequentie kon worden bepaald, bevatten varianten van de oorspronkelijke stam.
  • De werkzaamheid van het vaccin was 69,5% (95% betrouwbaarheidsinterval , 56,7 tot 78,8) tegen elke symptomatische Covid-19 veroorzaakt door vijf varianten die werden geïdentificeerd door sequencing.
  • In een post-hocanalyse was de werkzaamheid van het vaccin 78,8% (95% BI, 55,8 tot 90,8) tegen matige tot ernstige ziekte en 74,0% (95% BI, 62,1 tot 82,5) bij de deelnemers die seronegatief waren bij baseline.
  • Er deden zich geen ernstige gevallen van Covid-19 voor in de vaccingroep, waarin de mediane virale belasting voor doorbraakgevallen een factor meer dan 100 lager was dan die in de placebogroep.
  • De gevraagde bijwerkingen waren meestal licht of matig en van voorbijgaande aard en waren vaker in de vaccingroep dan in de placebogroep; lokale bijwerkingen kwamen voor bij respectievelijk 92,3% en 45,5% van de deelnemers, en systemische bijwerkingen bij 87,3% en 65,0%.
  • De incidentie van ongewenste bijwerkingen was vergelijkbaar in de twee groepen tot 21 dagen na elke dosis (22,7% en 20,4%) en van dag 43 tot dag 201 (4,2% en 4,0%).

Zo was de studie opgebouwd, zie in Figure 1




Figure 1. Enrollment, Randomization, and Analysis Populations.The data-cutoff date for the primary vaccine efficacy analysis was August 20, 2021. Of the 25,170 participants who were recruited, 24,141 underwent randomization in the intention-to-treat population. These participants had no virologic evidence of Covid-19 before receiving the trial injection. The safety population included 24,076 participants who had received one or more trial injections. The per-protocol population included 20,090 participants who had received two trial injections as scheduled and had no major protocol deviations. Participants may have discontinued their involvement in the trial after qualification as part of the per-protocol population (shown in the bottom set of boxes). An additional 10 participants withdrew from the study (4 in the vaccine group and 6 in the placebo group), and the timing of their discontinuation (by day 21, by day 42, or after day 42) could not be ascertained with confidence.


Het originele studierapport is volledig gratis in te zien. Klik daarvoor op de titel van het abstract:

June 2, 2022
N Engl J Med 2022; 386:2084-2096
DOI: 10.1056/NEJMoa2201300

Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

List of authors.
  • Karen J. Hager, M.Sc., 
  • Gonzalo Pérez Marc, M.D., 
  • Philipe Gobeil, Ph.D., 
  • Ricardo S. Diaz, M.D., 
  • Gretchen Heizer, M.Sc., 
  • Conrado Llapur, M.D., 
  • Alexander I. Makarkov, Ph.D., 
  • Eduardo Vasconcellos, M.D., 
  • Stéphane Pillet, Ph.D., 
  • Fernando Riera, M.D., 
  • Pooja Saxena, Ph.D., 
  • Priscila Geller Wolff, M.D., 
  •  for the CoVLP Study Team*

Abstract

BACKGROUND

Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 ) to form the candidate vaccine.

METHODS

In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.

RESULTS

A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval , 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).

CONCLUSIONS

The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697. opens in new tab.)


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