Covid-19 Living Data

Trial NCT04452318
Publication O'Brien M, N Engl J Med, 2021
Dates: 7/13/2020 to 1/28/2021
Funding: Mixed (Regeneron Pharmaceuticals; F. Hoffmann-La Roche; COVID-19 Prevention Network (CoVPN); National Institute of Allergy and Infectious Diseases, NIH)
Conflict of interest:

Methods
	RCT
	Location : Multicenter / Moldova, Romania, USA Follow-up duration (days): 28
Inclusion criteria	Adult participants 18 years of age (irrespective of weight) and above at the signing of informed consent or adolescent participants ?12 to <18 years of age, or pediatric participants <12 years of age at the signing of the assent (parent/guardian sign the informed consent) ; Asymptomatic household contact with exposure to an individual with a diagnosis of SARS-CoV-2 infection (index case). To be included in the study, participants must be randomized within 96 hours of collection of the index cases positive SARS-COV-2 diagnostic test sample ; Participant anticipates living in the same household with the index case until study day 29 ; Is judged by the investigator to be in good health based on medical history and physical examination at screening/baseline, including participants who are healthy or have a chronic, stable medical condition ; Willing and able to comply with study visits and study-related procedures/assessments ; Provide informed consent signed by study participant or legally acceptable representative
Exclusion criteria	Participant-reported history of prior positive SARS-CoV-2 RT-PCR test or positive SARS CoV-2 serology test at any time before the screening ; Participant has lived with individuals who have had previous SARS-CoV-2 infection or currently lives with individuals who have SARS-CoV-2 infection, with the exception of the index case(s), the first individual(s) known to be infected in the household ; Active respiratory or non-respiratory symptoms consistent with COVID-19 ; History of respiratory illness with sign/symptoms of SARS-CoV-2 infection, in the opinion of the investigator, within the prior 6 months to screening ; Nursing home resident ; Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study ; Current hospitalization or was hospitalized (i.e.,>24hours) for any reason within 30 days of the screening visit ; Has a history of significant multiple and/or severe allergies (e.g.,latexgloves), or has had an anaphylactic reaction to prescription or non-prescription drugs or food. This is to avoid possible confounding of the safety analysis and not due to any presumed increased risk of these individuals to a reaction to the investigational product ; Treatment with another investigational agent in the last 30 days or within five half-lives of the investigational drug, whichever is longer, prior to the screening visit ; Received an investigational or approved SARS-CoV-2 vaccine ; Received investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis (e.g., convalescent plasma or sera, monoclonal antibodies, hyperimmune globulin) ; Use of hydroxychloroquine/chloroquine for prophylaxis/treatment of SARS-CoV-2 or anti-SARS-viral agents,* e.g., remdesivir, within 60 days of screening Hydroxychloroquine/chloroquine for other uses, e.g.,, for use in autoimmune diseases, is allowed ; Member of the clinical site study team and/or immediate family ; Exclusion criterion #14 excluding sexually active men who are unwilling to use the following forms of medically acceptable birth control during the study drug follow-up period and for 8 months after single dose of study drug was removed since enrollment was expanded to include all women in protocol amendment 4 ; Exclusion criterion #15 excluding pregnant or breastfeeding women was removed since enrollment was expanded to all women in protocol amendment 4 ; Exclusion criterion #16 excluding women of childbearing potential (WOCBP) and girls at or beyond menarche (?12 to <18 years of age) who were unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 8 months after the last dose was removed since enrollment was expanded to all women in protocol amendment 4 *WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy
Interventions
	Treatment Casirivimab+Imdevimab (REGN-COV2) (*) Duration : Once-off
	Control Placebo
Participants
	Randomized 2475 participants (n₁=1240 / n₂= 1235)
	Characteristics of participants N=2475 Mean age : 43 691 males
Primary outcome
	In the register Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) during the EAP [ Time Frame: Up to 1 month ]; Proportion of participants with treatment-emergent adverse events (TEAEs) and severity of TEAEs [ Time Frame: Up to 8 months ]
	In the report
Documents available	Protocol Yes Statistical plan Yes Data-sharing stated Yes
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	Low
General comment	In addition to all versions of the published/pre-print article, the prospective registry (June 2020), protocol, statistical analysis plan and supplementary material were used in data extraction and assessment of risk of bias. The original phase 1-3 protocol was available. There were no substantive differences between the population, procedures, interventions or outcomes in the pre-print article and the registry. The article reports the primary results of the phase 3 multicenter two-part trial in adults and adolescents to prevent SARS-CoV-2 infection among uninfected household contacts (ie. RT-qPCR–negative at baseline) of infected individuals; a second part reports results in recently infected asymptomatic patients (ie. RT-qPCR–positive at baseline). These populations were mutually exclusive and analyzed separately. This trial was updated on August 13th, 2021 with data from the peer-reviewed publication.