REGEN-COV Antibody Combination in Outpatients With COVID-19 – Phase 1/2 Results
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Abstract
Background
Continued SARS-CoV-2 infections and COVID-19-related hospitalizations highlight the need for effective anti-viral treatments in the outpatient setting. In a descriptive interim analysis of the phase 1/2 portion of a double-blind phase 1/2/3 trial in COVID-19 outpatients conducted between June 16, 2020 and September 4, 2020, REGEN-COV ® (casirivimab plus imdevimab) antibody combination reduced SARS-CoV-2 viral load versus placebo.
Methods
This final phase 1/2 analysis comprises 799 outpatients, including 275 from the previous descriptive analysis (group-1) and 524 from phase 2 (group-2). Patients were randomized (1:1:1) to placebo, REGEN-COV 2400mg, or REGEN-COV 8000mg. Prespecified hierarchical analyses of virologic endpoints were performed in group-2. The proportion of patients with ≥1 COVID-19–related medically attended visit (MAV) through day 29 was assessed in group-1+2. Efficacy was assessed in patients confirmed SARS-CoV-2–positive by baseline nasopharyngeal RT-qPCR. Safety was assessed in all treated patients.
Results
Data from 799 outpatients enrolled from June 16, 2020 to September 23, 2020 are reported. Time-weighted average daily reduction in viral load through day 7 was significantly greater in the REGEN-COV combined 2400mg+8000mg group versus placebo in patients with baseline viral load >10 7 copies/mL (prespecified primary endpoint): -0.68 log 10 copies/ml (95% CI, -0.94 to -0.41; P <.0001). This reduction was - 0.73 ( P <.0001) and -0.36 ( P =.0003) log 10 copies/mL in serum antibody–negative patients and in the overall population, respectively. REGEN-COV reduced the proportion of patients with ≥1 COVID-19–related MAV versus placebo (2.8% [12/434] REGEN-COV combined dose group versus 6.5% [15/231] placebo; P =.024; relative risk reduction [RRR]=57%); in patients with ≥1 risk factor for hospitalization, the treatment effect was more pronounced (RRR=71%). Adverse events were similar across groups.
Conclusions
In COVID-19 outpatients enrolled prior to the widespread circulation of delta and omicron variants, treatment with REGEN-COV significantly reduced viral load and COVID-19–related MAVs.
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SciScore for 10.1101/2021.06.09.21257915: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The local institutional review board or ethics committee at each study center oversaw trial conduct and documentation.
Consent: All patients provided written informed consent before participating in the trial.Sex as a biological variable not detected. Randomization TRIAL DESIGN: This is an ongoing, adaptive, multicenter, randomized, double-blind, placebo-controlled, seamless phase 1/2/3 trial in Covid-19 outpatients (NCT04425629). Blinding The investigators, site personnel, and Regeneron were unaware of the treatment-group assignments. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources 15 All patients were assessed for the presence or absence of anti-SARS-CoV-2 … SciScore for 10.1101/2021.06.09.21257915: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The local institutional review board or ethics committee at each study center oversaw trial conduct and documentation.
Consent: All patients provided written informed consent before participating in the trial.Sex as a biological variable not detected. Randomization TRIAL DESIGN: This is an ongoing, adaptive, multicenter, randomized, double-blind, placebo-controlled, seamless phase 1/2/3 trial in Covid-19 outpatients (NCT04425629). Blinding The investigators, site personnel, and Regeneron were unaware of the treatment-group assignments. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources 15 All patients were assessed for the presence or absence of anti-SARS-CoV-2 antibodies: anti-spike [S1] IgA, anti-spike [S1] IgG, and anti-nucleocapsid IgG. antibodiessuggested: Noneanti-spikesuggested: Noneanti-nucleocapsid IgGsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analyses were performed with SAS software, version 9.4 or higher (SAS Institute). SASsuggested: (SASqPCR, RRID:SCR_003056)SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04425629 Recruiting Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-Co… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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