Effect of the Neutralizing SARS-CoV-2 Antibody Sotrovimab in Preventing Progression of COVID-19: A Randomized Clinical Trial

  1. Anil Gupta
  2. Yaneicy Gonzalez-Rojas
  3. Erick Juarez
  4. Manuel Crespo Casal
  5. Jaynier Moya
  6. Diego Rodrigues Falci
  7. Elias Sarkis
  8. Joel Solis
  9. Hanzhe Zheng
  10. Nicola Scott
  11. Andrea L. Cathcart
  12. Sergio Parra
  13. Jennifer E. Sager
  14. Daren Austin
  15. Amanda Peppercorn
  16. Elizabeth Alexander
  17. Wendy W. Yeh
  18. Cynthia Brinson
  19. Melissa Aldinger
  20. Adrienne E. Shapiro

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Abstract

Importance

Older patients and those with underlying comorbidities infected with SARS-CoV-2 may be at increased risk of hospitalization and death from COVID-19. Sotrovimab is a neutralizing antibody designed for treatment of high-risk patients to prevent COVID-19 progression.

Objective

To evaluate the efficacy and safety of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

Design

Randomized, double-blind, multicenter, placebo-controlled, phase 3 study.

Setting

57 centers in 5 countries.

Participants

Nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for disease progression.

Intervention

Patients were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo.

Main Outcomes and Measures

The primary efficacy outcome was the proportion of patients with COVID-19 progression, defined as all-cause hospitalization longer than 24 hours for acute illness management or death through day 29. Key secondary outcomes included the proportion of patients with COVID-19 progression, defined as emergency room visit, hospitalization of any duration, or death, and proportion of patients developing severe/critical respiratory COVID-19 requiring supplemental oxygen.

Results

Among 1057 patients randomized (sotrovimab, 528; placebo, 529), all-cause hospitalization longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) by 79% (95% CI, 50% to 91%; P <.001). Secondary outcome results further demonstrated the effect of sotrovimab in reducing emergency room visits, hospitalization of any duration, or death, which was reduced by 66% (95% CI, 37% to 81%; P <.001), and severe/critical respiratory COVID-19, which was reduced by 74% (95% CI, 41% to 88%; P =.002). No patients receiving sotrovimab required high-flow oxygen, oxygen via nonrebreather mask, or mechanical ventilation compared with 14 patients receiving placebo. The proportion of patients reporting adverse events was similar between treatment groups; sotrovimab was well tolerated, and no safety concerns were identified.

Conclusions and Relevance

Among nonhospitalized patients with mild to moderate COVID-19, a single 500-mg intravenous dose of sotrovimab prevented progression of COVID-19, with a reduction in hospitalization and need for supplemental oxygen. Sotrovimab is a well-tolerated, effective treatment option for patients at high risk for severe morbidity and mortality from COVID-19.

Trial Registration

ClinicalTrials.gov Identifier: NCT04545060

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.11.03.21265533: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consent was provided by all patients prior to study entry; patients did not receive a stipend.
    Sex as a biological variablenot detected.
    RandomizationStudy Design: The early treatment of mild to moderate COVID-19 with sotrovimab was assessed in this phase 3, randomized, double-blind, placebo-controlled, multicenter study.
    Blindingnot detected.
    Power AnalysisSample Size: A sample size of 1360 patients (680 per treatment group) was determined to provide approximately 90% power to detect a 37.5% relative efficacy in reducing COVID-19 progression through day 29 at the overall 2-sided 5% significance level.

    Table 2: Resources

    Antibodies
    SentencesResources
    AEs of special interest were defined as infusion-related reactions (including hypersensitivity reactions) and the potential for antibody-dependent enhancement.
    antibody-dependent enhancement.
    suggested: None

    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: We detected the following sentences addressing limitations in the study:
    This trial has several limitations. Given the profound efficacy of sotrovimab, a small number of events for the primary and clinical secondary outcomes were reported in patients who were randomized to sotrovimab. As a result, it is challenging to determine the patient or disease characteristics associated with COVID-19 progression in sotrovimab-treated patients. Also notable is that the moderate size of the safety population limits the ability to detect rare AEs. However, based on the development of sotrovimab from a human antibody engineered to target a viral epitope, rare AEs are not expected. Finally, the study enrolled patients over approximately 6 months, representing a finite period of the pandemic. As a result, the complete picture of viral sequencing and clinical experience with sotrovimab for variants of concern is unknown. Despite this, sotrovimab targets a viral epitope that does not overlap with mutations observed in current variants of concern, and thus it is hypothesized that sotrovimab will remain effective against these variants.19,45

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04545060CompletedVIR-7831 for the Early Treatment of COVID-19 in Outpatients

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.11.03.21265533v1 on medRxiv