Covid-19 Living Data

Trial NCT04426695
Publication Somersan-Karakaya S, J Infect Dis (2022) (published paper)
Dates: 2020-06-11 to 2021-04-09
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 / USA, Brazil, Chile, Mexico, Moldova, Romania Follow-up duration (days): 56
Inclusion criteria	Has provided informed consent (signed by study patient or legally acceptable representative) Male or female adult ≥18 years of age (or country’s legal age of adulthood if higher) at randomization Has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive antigen or molecular diagnostic test (by validated SARS CoV-2 antigen, reverse transcription polymerase chain reaction [RT-PCR], or other molecular diagnostic assay, using an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal, or saliva) ≤72 hours prior to randomization and no alternative explanation for current clinical condition. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable. Has symptoms consistent with coronavirus disease 2019 (Covid-19), as determined by investigator, with onset ≤10 days before randomization Hospitalized for ≤72 hours with at least 1 of the following at randomization patients meeting more than 1 criterion will be categorized in the most severely affected category: Cohort 1A (no supplemental oxygen): With Covid-19 symptoms but not requiring supplemental oxygen Cohort 1 (low-flow oxygen): Maintains O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device.
Exclusion criteria	In the opinion of the investigator, unlikely to survive for >48 hours from screening Receiving extracorporeal membrane oxygenation Has new-onset stroke or seizure disorder during hospitalization Initiated on renal replacement therapy due to Covid-19 Has circulatory shock requiring vasopressors at randomization Note: Patients who require vasopressors for sedation-related hypotension or reasons other than circulatory shock may be eligible in this study Patients who have received convalescent plasma, intravenous immunoglobulin (IVIG), or monoclonal antibodies against SARS-CoV-2 (e.g., bamlanivimab) within 5 months prior to randomization or plan to receive during the study period for any indication Participation in a clinical research study, including any double-blind study, evaluating an investigational product within 30 days and less than 5 half-lives of the investigational product prior to the screening visit Note: The use of remdesivir, hydroxychloroquine, or other treatments (except for Covid-19 convalescent plasma or IVIG) being used for Covid-19 treatments in the context of the local standard-of-care or an open-label study or compassionate use protocol is permitted Any physical examination findings, history of illness, and/or concomitant medications that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study Known allergy or hypersensitivity to components of study drug Pregnant or breastfeeding women Continued sexual activity in women of childbearing potential or sexually active men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
Interventions
	Treatment REGN-COV2 2400mg 1200 mg Casirivimab and 1200 mg Imdevimab intravenously single dose REGN-COV2 8000mg 4000 mg Casirivimab and 4000 mg Imdevimab intravenously single dose
	Control Placebo
Participants
	Randomized participants : Placebo=452 REGN-COV2 2400mg=457 REGN-COV2 8000mg=455
	Characteristics of participants N= 1364 Mean age : NR 647 males Severity : Mild: n=525 / Moderate: n=671 / Severe: n=1 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register 1) Time-weighted average change from baseline in viral load as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline to Day 7 ]; 2) Proportion of patients who died or required mechanical ventilation [ Time Frame: Day 6 through Day 29 ]; 3) Proportion of patients who died or required mechanical ventilation [ Time Frame: Day 1 through Day 29 ]; 4) Incidence of patients who died or required mechanical ventilation [ Time Frame: Up to day 29 ]; 5) Proportion of patients with treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Through Day 169 ] 6) Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]; 7) Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]
	In the report 1) Primary virologic efficacy endpoint - time-weighted average (TWA) daily change from baseline (day 1) viral load in nasopharyngeal samples through day 7; 2) Primary clinical efficacy endpoint - proportion of patients who died or required mechanical ventilation from day 6-29 and day 1-29.
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 all versions of the pre-print article, the prospective trial registry, protocol (obtained from contact with authors), and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. Only three of seven primary outcomes in the registry are described as primary outcomes in the article. Otherwise, there were no important differences between the registry and the article. The trial was terminated early due to slow recruitment and did not achieve its target sample size. This study was updated on the March 2nd, 2022 with data extracted from the fourth version of the preprint. This study was updated on the May 9th, 2022 with data obtained from contact with authors. This study was further updated on September 1st, 2022 after publication of the study report.