Covid-19 Living Data

Trial NCT04452318
Publication O'Brien M, JAMA (2022) (published paper)
Dates: 2020-07-13 to 2021-01-28
Funding: Mixed (Regeneron Pharmaceuticals, Inc.; F. Hoffmann-La Roche Ltd.; COVID-19 Prevention Network (CoVPN) )
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Moldova, Romania, USA Follow-up duration (days): 226
Inclusion criteria	Adults (aged ≥18 years) and adolescents (aged ≥12 to <18 years) Were household contacts of the first known household member with SARS-CoV-2 infection (index case) and who were asymptomatic (having no active respiratory or nonrespiratory symptoms consistent with COVID-19) Part B participants were SARS-CoV-2 positive by RT-qPCR central laboratory testing. COVID-19 vaccination was prohibited prior to enrollment but was allowed after completing the 28-day efficacy assessment period.
Exclusion criteria	Taken verbatim from the supplementary appendix (includes criteria for Part A and Part B) 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., >24 hours) for any reason within 30 days of the screening visit Has a history of significant multiple and/or severe allergies (e.g.,latex gloves),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 5 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, ego, 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
Interventions
	Treatment REGN-COV2 1200 mg subcutaneously once-off on day 1
	Control Placebo
Participants
	Randomized participants : REGN-COV2=156 Placebo=158
	Characteristics of participants N= 314 Mean age : NR 141 males Severity : Mild: n= 0/ Asymptomatic: n=314 Number of vaccinated participants: NR
Primary outcome
	In the register Proportion of participants who subsequently develop signs and symptoms (broad-term) within 14 days of a positive RT-qPCR at baseline or during the EAP [ Time Frame: Up to 1 month ]
	In the report The proportion of participants who had a positive RT-qPCR result at baseline or during the 28-day efficacy assessment period and who developed signs and symptoms of COVID-19 within 14 days of the positive RT-qPCR result.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: 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	Some concerns
General comment	In addition to the published report, the 2 versions of the pre-print article, the prospective registry (2020-06-30), protocol and supplementary appendices (including supplementary methods and statistical analysis methods) 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 supplementary appendices and the final registry. Considerable changes were made to outcomes in the registry during and after the trial, but these do not affect the data extracted. The article reports the adult/adolescent treatment part of a larger two-part trial that includes both treatment of asymptomatic RT-PCR-positive COVID patients (adults/adolescents and children) to prevent development of symptoms and prophylaxis in RT-PCR-negative contacts (adults/adolescents and children) of confirmed cases. The article also reports the proportion of participants who had a hospitalization related to a confirmed SARS-CoV-2 infection up to day 29. This was used in the composite hospitalization or death outcome extracted. Of note, "the trial was ongoing at the time of this report, so while all participants completed the 28-day efficacy assessment period, some were early in the follow-up period". Hence, all data were extracted under the day 28 timepoint until the updated completed report is available. This study was updated on October 6th, 2021 with data from the updated pre-print article and data gained from contact with authors. This study was updated on March 2nd, 2022 with data from the published report.