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Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial.
Herman, Gary A; O'Brien, Meagan P; Forleo-Neto, Eduardo; Sarkar, Neena; Isa, Flonza; Hou, Peijie; Chan, Kuo-Chen; Bar, Katharine J; Barnabas, Ruanne V; Barouch, Dan H; Cohen, Myron S; Hurt, Christopher B; Burwen, Dale R; Marovich, Mary A; Musser, Bret J; Davis, John D; Turner, Kenneth C; Mahmood, Adnan; Hooper, Andrea T; Hamilton, Jennifer D; Parrino, Janie; Subramaniam, Danise; Baum, Alina; Kyratsous, Christos A; DiCioccio, A Thomas; Stahl, Neil; Braunstein, Ned; Yancopoulos, George D; Weinreich, David M.
  • Herman GA; Regeneron Pharmaceuticals, Tarrytown, NY, USA. Electronic address: gary.herman@regeneron.com.
  • O'Brien MP; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Forleo-Neto E; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Sarkar N; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Isa F; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Hou P; Formerly of Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Chan KC; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Bar KJ; Department of Medicine and Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
  • Barnabas RV; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Division of Allergy and Infectious Diseases and Department of Epidemiology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Cohen MS; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hurt CB; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Burwen DR; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • Marovich MA; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • Musser BJ; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Davis JD; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Turner KC; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Mahmood A; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Hooper AT; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Hamilton JD; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Parrino J; Formerly of Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Subramaniam D; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Baum A; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Kyratsous CA; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • DiCioccio AT; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Stahl N; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Braunstein N; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Yancopoulos GD; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Weinreich DM; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Lancet Infect Dis ; 22(10): 1444-1454, 2022 10.
Article in English | MEDLINE | ID: covidwho-1915194
ABSTRACT

BACKGROUND:

There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2-8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings.

METHODS:

This was a randomised, double-blind, placebo-controlled trial done in the USA, Romania, and Moldova in 2020-2021, before the emergence of omicron (B.1.1.529) and omicron-lineage variants. Uninfected and unvaccinated household contacts of infected individuals, judged by the investigator to be in good health, were randomly assigned (11) to receive 1200 mg CAS + IMD or placebo by subcutaneous injection according to a central randomisation scheme provided by an interactive web response system; randomisation was stratified per site by the test results of a local diagnostic assay for SARS-CoV-2 and age group at baseline. COVID-19 vaccines were prohibited before randomisation, but participants were allowed to receive COVID-19 vaccination during the follow-up period. Participants who developed COVID-19 symptoms during the follow-up period underwent RT-PCR testing. Prespecified endpoints included the proportion of previously uninfected and baseline-seronegative participants (seronegative-modified full analysis set) who had RT-PCR-confirmed COVID-19 in the follow-up period (post-hoc for the timepoints of months 2-5 and 6-8 only) and underwent seroconversion (ie, became seropositive, considered a proxy for any SARS-CoV-2 infections [symptomatic and asymptomatic]; prespecified up to day 57, post-hoc for all timepoints thereafter). We also assessed the incidence of treatment-emergent adverse events. This study is registered with ClinicalTrials.gov, NCT04452318.

FINDINGS:

From July 13, 2020, to Oct 4, 2021, 2317 participants who were RT-PCR-negative for SARS-CoV-2 were randomly assigned, of whom 1683 (841 assigned to CAS + IMD and 842 assigned to placebo) were seronegative at baseline. During the entirety of the 8-month study, CAS + IMD reduced the risk of COVID-19 by 81·2% (nominal p<0·0001) versus placebo (prespecified analysis). During the 7-month follow-up period, protection was greatest during months 2-5, with a 100% relative risk reduction in COVID-19 (nominal p<0·0001; post-hoc analysis). Efficacy waned during months 6-8 (post-hoc analysis). Seroconversion occurred in 38 (4·5%) of 841 participants in the CAS + IMD group and in 181 (21·5%) of 842 in the placebo group during the 8-month study (79·0% relative risk reduction vs placebo; nominal p<0·0001). Six participants in the placebo group were hospitalised due to COVID-19 versus none who received CAS + IMD. Serious treatment-emergent adverse events (including COVID-19) were reported in 24 (1·7%) of 1439 participants receiving CAS + IMD and in 23 (1·6%) of 1428 receiving placebo. Five deaths were reported, none of which were due to COVID-19 or related to the study drugs.

INTERPRETATION:

CAS + IMD is not authorised in any US region as of Jan 24, 2022, because data show that CAS + IMD is not active against omicron-lineage variants. In this study, done before the emergence of omicron-lineage variants, a single subcutaneous 1200 mg dose of CAS + IMD protected against COVID-19 for up to 5 months of community exposure to susceptible strains of SARS-CoV-2 in the pre-exposure prophylaxis setting, in addition to the post-exposure prophylaxis setting that was previously shown.

FUNDING:

Regeneron Pharmaceuticals, F Hoffmann-La Roche, US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Diagnostic study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Language: English Journal: Lancet Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Diagnostic study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Language: English Journal: Lancet Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article