Covid-19 Living Data

Trial NCT04666441
Publication Portal Celhay C, JAMA Netw Open (2022) (results posted on registry)
Dates: 2020-12-15 to 2021-02-26
Funding: Private (Regeneron Pharmaceuticals, Inc, and Hoffman-La Roche. Employees of Regeneron Pharmaceuticals participated in the development and review of the manuscript.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 169
Inclusion criteria	Outpatients Aged 18 years and older Positive SARS-CoV-2 diagnostic test (using a local SARS-CoV-2 antigen, quantitative reverse transcription–polymerase chain reaction [RT-qPCR], or other molecular diagnostic assay) from a sample (such as NP, nasal, oropharyngeal, or saliva) collected within 72 hours prior to randomization Either asymptomatic or symptomatic within 7 days before randomization Eligible symptomatic patients were required to be at low risk for developing severe COVID-19, defined as meeting all the following criteria: Body mass index (calculated as weight in kilograms divided by height in meters squared) less than 30 Age 50 years or younger Not pregnant No cardiovascular disease or hypertension, chronic lung disease or asthma, type 1 or 2 diabetes, chronic kidney disease, or chronic liver disease Eligible asymptomatic patients, with or without risk factors, could not have symptoms consistent with COVID-19 currently or at any time within 2 months and could not have received a COVID-19 vaccination prior to randomization The presence or absence of COVID-19 symptoms was determined at the discretion of investigators
Exclusion criteria	Immunosuppressed patients Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2, 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). Note: prior use is defined as the past 30 days or within than 5 half-lives of the investigational product (whichever is longer) from screening Prior use (prior to randomization), current use (at randomization), or planned use (within time period given per CDC guidance but no sooner than 22 days of study drug administration) of any authorized or approved vaccine for COVID-19. Note: As of 02 March 2021, CDC guidance recommends deferral of SARS-CoV-2 vaccination for at least 90 days after administration of passive antibody therapy Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test Has known allergy or hypersensitivity to components of study drug Has been discharged, or is planned to be discharged, to a quarantine center Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19 Is a member of the clinical site study team or is an immediate family member of the site study team
Interventions
	Treatment REGN-COV2 2400mg Casirivimab 1200 mg + Imdevimab 1200 mg intravenously single dose REGN-COV2 1200mg Casirivimab 600 mg + Imdevimab 600 mg intravenously single dose
	Control Placebo
Participants
	Randomized participants : Placebo=82 REGN-COV2 2400mg=166 REGN-COV2 1200mg=165
	Characteristics of participants N= 413 Mean age : NR 219 males Severity : Mild: n= / Asymptomatic: n= Number of vaccinated participants: 0
Primary outcome
	In the register Time-Weighted Average Daily Change From Day 1 in Viral Load in NP Swab Samples [ Time Frame: Day 1 to Day 7 ] Time-weighted average daily change from Day 1 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
	In the report Time-weighted average daily change from baseline (TWACB) in viral load (log10 copies per milliliter) to day 7, as measured by RT-qPCR of NP swab samples in patients who had a central laboratory–determined RT-qPCR positive test at baseline and were seronegative (ie, negative for anti-spike [S1] IgA, anti-spike [S1] IgG, and anti-nucleocapsid IgG)
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: N
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 the published article, the protocol, statistical analysis plan, supplemental materials and study registry were used in data extraction and risk of bias assessment. Only the interventions and placebo arms given IV were extracted. Registry posted results were extracted as the report published only interim results (at day 7, early database lock in Feb 2021, whereas the registry has longer follow-up results, posted Apr 2022, and reports on a larger sample size). The registry primary outcome reflects the reported primary outcome. Some outcomes (e.g. total adverse events, serious adverse events, mortality) are reported in the paper, and were pre-specified in the protocol but not the registry. Adverse events were reported in the publication reporting interim results but were not extractable from the registry with longer follow up. Viral negative conversion event were reported as well but data was presented for the pooled IV/SC placebo and could not be extracted.