Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

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  • O'Brien, M.P.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Forleo-Neto, E.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Sarkar, N.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Isa, F.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Hou, P.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Chan, K.-C.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Musser, B.J.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Bar, K.J.
    • Other Affiliation: University of Pennsylvania
  • Barnabas, R.V.
    • Other Affiliation: University of Washington
  • Barouch, D.H.
    • Other Affiliation: Harvard Medical School
  • Cohen, M.S.
  • Hurt, C.B.
  • Burwen, D.R.
    • Other Affiliation: National Institutes of Health
  • Marovich, M.A.
    • Other Affiliation: National Institutes of Health
  • Brown, E.R.
    • Other Affiliation: University of Washington
  • Heirman, I.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Davis, J.D.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Turner, K.C.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Ramesh, D.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Mahmood, A.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Hooper, A.T.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Hamilton, J.D.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Kim, Y.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Purcell, L.A.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Baum, A.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Kyratsous, C.A.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Krainson, J.
    • Other Affiliation: Clinical Trials of Florida LLC
  • Perez-Perez, R.
    • Other Affiliation: Medical Research of Westchester
  • Mohseni, R.
    • Other Affiliation: Catalina Research Institute LLC
  • Kowal, B.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Dicioccio, A.T.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Geba, G.P.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Stahl, N.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Lipsich, L.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Braunstein, N.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Herman, G.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Yancopoulos, G.D.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
  • Weinreich, D.M.
    • Other Affiliation: Regeneron Pharmaceuticals Inc
Abstract
  • Importance: Easy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage. Objective: To evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2-infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020-January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) testing are reported. Interventions: Individuals were randomized 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156). Main Outcomes and Measures: The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10copies/mL). Results: Among 314 randomized participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P =.04; absolute risk difference, -13.3% [95% CI, -26.3% to -0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P =.03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P =.001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19. Conclusions and Relevance: Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04452318.
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  • Article
Rights statement
  • In Copyright
Journal title
  • JAMA - Journal of the American Medical Association
Journal volume
  • 327
Journal issue
  • 5
Page start
  • 432
Page end
  • 441
Language
  • English
ISSN
  • 0098-7484
Publisher
  • American Medical Association

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