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
Creators: name: Hurt, Christopher B
name: Braunstein, Ned
name: Turner, Kenneth C
name: Sarkar, Neena
name: Cohen, Myron S
name: Mahmood, Adnan
name: Forleo-Neto, Eduardo
name: O'Brien, Meagan P
name: Weinreich, David M
name: Kyratsous, Christos A
name: Barouch, Dan H
name: Marovich, Mary A
name: Bar, Katharine J
name: Davis, John D
name: Parrino, Janie
name: Stahl, Neil
name: Herman, Gary A
name: Hou, Peijie
name: Yancopoulos, George D
name: Hamilton, Jennifer D
name: COVID-19 Phase 3 Prevention Trial Team
name: DiCioccio, A Thomas
name: Chan, Kuo-Chen
name: Musser, Bret J
name: Subramaniam, Danise
name: Burwen, Dale R
name: Baum, Alina
name: Barnabas, Ruanne V
name: Isa, Flonza
name: Hooper, Andrea T
Publisher: name: Elsevier
Year: 2022

description: <p>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&thinsp;+&thinsp;IMD) prevented symptomatic SARS-CoV-2 infections by 81&middot;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 (1:1) to receive 1200 mg CAS&thinsp;+&thinsp;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&thinsp;+&thinsp;IMD and 842 assigned to placebo) were seronegative at baseline. During the entirety of the 8-month study, CAS&thinsp;+&thinsp;IMD reduced the risk of COVID-19 by 81&middot;2% (nominal p&lt;0&middot;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&lt;0&middot;0001; post-hoc analysis). Efficacy waned during months 6-8 (post-hoc analysis). Seroconversion occurred in 38 (4&middot;5%) of 841 participants in the CAS&thinsp;+&thinsp;IMD group and in 181 (21&middot;5%) of 842 in the placebo group during the 8-month study (79&middot;0% relative risk reduction vs placebo; nominal p&lt;0&middot;0001). Six participants in the placebo group were hospitalised due to COVID-19 versus none who received CAS&thinsp;+&thinsp;IMD. Serious treatment-emergent adverse events (including COVID-19) were reported in 24 (1&middot;7%) of 1439 participants receiving CAS&thinsp;+&thinsp;IMD and in 23 (1&middot;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&thinsp;+&thinsp;IMD is not authorised in any US region as of Jan 24, 2022, because data show that CAS&thinsp;+&thinsp;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&thinsp;+&thinsp;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.</p>