Covid-19 Living Data

Trial NCT04425629
Publication Weinreich D, N Engl J Med, 2021 (published paper)
Dates: 2020-09-24 to 2021-01-17
Funding: Mixed (Regeneron Pharmaceuticals, Inc.; Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Mexico, USA Follow-up duration (days): 28
Inclusion criteria	≥18 years of age; Non-hospitalized; Confirmed local SARS-CoV-2-positive diagnostic test result ≤72 hours and onset of any Covid-19 symptom as determined by the investigator, ≤7 days before randomization; ≥1 risk factor for severe Covid-19.
Exclusion criteria	Admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization; Participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit; Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational); Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19; Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19
Interventions
	Treatment Casirivimab+Imdevimab (REGN-COV2) 2400mg 2400 mg IV once-off on day 1
	Control Placebo
Participants
	Randomized 3029 participants (n₁=1529 / n₂= 1500)
	Characteristics of participants N=3029 Mean age : NR 1289 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=0 Critical: n=0
Primary outcome
	In the register Proportion of patients with at least one (≥1) COVID-19-related hospitalization or all-cause death [ Time Frame: Through Day 29 ]
	In the report The proportion of patients with ≥1 Covid-19-related hospitalization or all-cause death through day 29
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated No
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the pre-print article, the prospective study registry, the supplementary appendices, protocol and statistical analysis plan were used in data extraction and risk of bias assessment. The overall study was a phase 1/2/3 trial recruiting 3 cohorts of COVID-19 outpatients: patients ≥18 years, patients <18 years, and patients pregnant at randomization. Initially, patients were randomized to receive either IV placebo, REGEN-COV 2400mg (1200mg each of casirivimab and imdevimab), or REGEN-COV 8000mg (4000mg each antibody). Based upon phase 1/2 results, the trial was amended so that subsequent patients enrolled all had ≥1 risk factor for severe Covid-19 and were randomized to receive either IV placebo, REGEN-COV 1200mg (600mg each antibody) IV, or REGEN-COV 2400mg. In February 2021, an independent data monitoring committee recommended stopping enrolment of patients into the placebo group because the accumulated data indicated efficacy of REGEN-COV. The reported analysis included only patients ≥ 18 years of age with ≥1 risk factor for severe COVID-19, randomized to REGEN-COV 2400mg or 1200mg, with their concurrent placebo groups serving as a control. Patients randomized in the early stages of the trial who had no risk factors for severe COVID-19 were excluded from analyses. There is no change from the trial registration in the intervention and control treatments. The primary outcomes indicated in the registry reflects the primary outcome reported in the paper. Some outcomes from the registry are not reported in the paper (e.g., proportion of participants requiring supplemental oxygen due to COVID-19 by day 29, all-cause death by day 120).