VIR-7831 for the Early Treatment of COVID-19 in Outpatients (COMET-ICE)

A Phase II/III Randomized, Multi-center, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Monoclonal Antibody VIR-7831 for the Early Treatment of Coronavirus Disease 2019 (COVID-19) in Non-hospitalized Patients

This is a phase 2/3 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and will be assessed for safety, tolerability, efficacy, and pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: VIR-7831 (sotrovimab); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1057
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Investigative Site
  • Vienna, Austria, 1100
    • Investigative Site
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30110-934
      • Investigative Site
  • Parana
    • Maringá, Parana, Brazil, 87083-240
      • Investigative Site
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 590250-50
      • Investigative Site
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-120
      • Investigative Site
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Investigative Site
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Investigative Site
  • Santa Catarina
    • Chapecó, Santa Catarina, Brazil, 89801-355
      • Investigative Site
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09030-010
      • Investigative Site
    • Vila Assuncao, Sao Paulo, Brazil, 05615-190
      • Investigative Site
  • São Paulo
    • Campinas, São Paulo, Brazil, 13060-904
      • Investigative Site
• Canada
  • Ontario
    • Sarnia, Ontario, Canada, N7T 4X3
      • Investigative Site
    • Toronto, Ontario, Canada, M9V 4B4
      • Investigative Site
  • Quebec
    • Québec, Quebec, Canada, G2J0C4
      • Investigative Site
• Peru
  • Bella Vista, Peru, 07006
    • Investigative Site
  • Lima, Peru, 15082
    • Investigative Site
  • Callao
    • Bellavista, Callao, Peru, 7016
      • Investigative Site
  • Lima
    • El Agustino, Lima, Peru, 15007
      • Investigative Site
    • Huaral, Lima, Peru, 15131
      • Investigative Site
    • San Isidro, Lima, Peru, 15036
      • Investigative Site
• Spain
  • Albacete, Spain, 02006
    • Investigative Site
  • Girona, Spain, 17005
    • Investigative Site
  • Granada, Spain, 18014
    • Investigative Site
  • Vigo, Spain, 36312
    • Investigative Site
  • Barcelona
    • Centelles, Barcelona, Spain, 08540
      • Investigative Site
    • Terrassa, Barcelona, Spain, 08221
      • Investigative Site
• United Kingdom
  • Belfast, United Kingdom, BT7 2EB
    • Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Investigative Site
    • Cullman, Alabama, United States, 35055
      • Investigative Site
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Investigative Site
    • Tucson, Arizona, United States, 85712
      • Investigative Site
  • California
    • Los Angeles, California, United States, 90036
      • Investigative Site
    • Los Angeles, California, United States, 90017
      • Investigative Site
    • Northridge, California, United States, 91325
      • Investigative Site
    • Oxnard, California, United States, 93030
      • Investigative Site
    • Rolling Hills Estates, California, United States, 90274
      • Investigative Site
    • Sacramento, California, United States, 95817
      • Investigative Site
  • Florida
    • Doral, Florida, United States, 33166
      • Investigative Site
    • Gainesville, Florida, United States, 32607
      • Investigative Site
    • Hialeah, Florida, United States, 33016
      • Investigative Site
    • Miami, Florida, United States, 33125
      • Investigative Site
    • Miami, Florida, United States, 33155
      • Investigative Site
    • Miami, Florida, United States, 33186
      • Investigative Site
    • Miami, Florida, United States, 33122
      • Investigative Site
    • Miami, Florida, United States, 33173
      • Investigative Site
    • Miramar, Florida, United States, 33027
      • Investigative Site
    • North Miami, Florida, United States, 33169
      • Investigative Site
    • Palmetto Bay, Florida, United States, 33157
      • Investigative Site
    • Pembroke Pines, Florida, United States, 33024
      • Investigative Site
    • Pompano Beach, Florida, United States, 33064
      • Investigative Site
    • Tampa, Florida, United States, 33614
      • Investigative Site
    • Tampa, Florida, United States, 33615
      • Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30315
      • Investigative Site
    • Atlanta, Georgia, United States, 30318
      • Investigative Site
    • Decatur, Georgia, United States, 30030
      • Investigative Site
    • Stockbridge, Georgia, United States, 30281
      • Investigative Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Investigative Site
  • Indiana
    • Mishawaka, Indiana, United States, 46544
      • Investigative Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Investigative Site
    • Marrero, Louisiana, United States, 70072
      • Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21230
      • Investigative Site
  • Michigan
    • Caro, Michigan, United States, 48723
      • Investigative Site
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Investigative Site
    • Las Vegas, Nevada, United States, 89130
      • Investigative Site
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Investigative Site
  • New York
    • Bronx, New York, United States, 10456
      • Investigative Site
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Investigative Site
    • Charlotte, North Carolina, United States, 28208
      • Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Investigative Site
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Investigative Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Investigative Site
  • Texas
    • Austin, Texas, United States, 78705
      • Investigative Site
    • Baytown, Texas, United States, 77521
      • Investigative Site
    • Beaumont, Texas, United States, 77702
      • Investigative Site
    • Dallas, Texas, United States, 75231
      • Investigative Site
    • Denton, Texas, United States, 76210
      • Investigative Site
    • El Paso, Texas, United States, 79935
      • Investigative Site
    • Forney, Texas, United States, 75126
      • Investigative Site
    • Houston, Texas, United States, 77090
      • Investigative Site
    • Houston, Texas, United States, 77058
      • Investigative Site
    • Houston, Texas, United States, 77017
      • Investigative Site
    • Houston, Texas, United States, 77024
      • Investigative Site
    • Humble, Texas, United States, 77338
      • Investigative Site
    • Laredo, Texas, United States, 78041
      • Investigative Site
    • McAllen, Texas, United States, 78504
      • Investigative Site
    • Mesquite, Texas, United States, 75149
      • Investigative Site
    • Sugar Land, Texas, United States, 77478
      • Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Investigative Site
    • Seattle, Washington, United States, 98109
      • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be aged 18 years or older AND at high risk of progression of COVID-19 or ≥ 55 years old
• Participants must have a positive SARS-CoV-2 test result and oxygen saturation ≥94% on room air and have COVID-19 symptoms and be less than or equal to 5 days from onset of symptoms

Exclusion Criteria:

• Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours
• Symptoms consistent with severe COVID-19
• Participants who, in the judgement of the investigator are likely to die in the next 7 days
• Severely immunocompromised participants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VIR-7831 (Sotrovimab); Participants received 500 mg sotrovimab administered intravenously (IV)	Biological: VIR-7831 (sotrovimab); VIR-7831 (sotrovimab) given by intravenous infusion (single dose)
Placebo Comparator: Placebo; Participants received placebo administered intravenously (IV)	Drug: Placebo; Sterile normal saline (0.9% NaCl) given by intravenous infusion (single dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Progression of COVID-19 Through Day 29	COVID-19 progression defined as hospitalization >24 hours or death	Through Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)		Up to 24 weeks
Number of Participants With Serious Adverse Events (SAEs)		Up to 24 weeks
Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions		Up to 24 weeks
Number of Participants With Cardiac Events of Special Interest		Up to 24 weeks
Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab		Up to 24 weeks
Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab	Titers defined as the reciprocal of the highest dilution of the sample (including minimum required dilution) that yields a positive result.	Up to 24 Weeks
Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Concentration at the Last Quantifiable Time Point (Clast) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Time to Reach the Maximum Concentration (Tmax) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUCinf) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Area Under the Serum Concentration-time Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Percentage of AUCinf Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Apparent Volume of Distribution During the Elimination Phase (Vz) of VIR-7831 Following IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 Following IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Clearance (CL) of VIR-7831 After IV Administration		Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Number of Participants Who Had Progression of COVID-19	COVID-19 progression defined as a visit to a hospital emergency room for management of illness or hospitalization for acute management of illness or death	Through Day 29
Mean Change in FLU PRO Plus Total Score (AUC)	Mean change in InFLUenza Patient-Reported Outcome (FLU-PRO Plus) questionnaire total score. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste. The mean total score can range from 0 (symptom free) to 4 (very severe symptoms) and was calculated as the arithmetic mean of the 32 items within FLU-PRO. Missing total score at day 7 was imputed using a modified last observation carried forward approach.	Through Day 7
Time to Symptom Alleviation Using FLU-PRO Plus	Symptom alleviation is defined as absence of the majority of core symptoms of COVID-19 (except for cough or fatigue, where scoring no more than 'somewhat' in severity, and loss of smell or taste were allowed) as measured by FLU-PRO Plus, sustained for >=48 hours. Participants could only achieve sustained symptom alleviation following >=2 non-missing consecutively scored questionnaires that showed symptom alleviation. Participants who did not achieve sustained symptom alleviation were censored at Day 21, the day of death, or the day of withdrawal, whichever was earliest. Days where symptom alleviation could not be assessed to a missing/incomplete questionnaire were imputed as no symptom alleviation. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste.	Through Day 21
Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8		Baseline and Day 8
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 8		Through Day 8
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 15	Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.	Through Day 15
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 22	Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.	Through Day 22
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 29	Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.	Through Day 29
29-day All-cause Mortality	Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal	Through Day 29
60-day All-cause Mortality	Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal	Through Day 60
90-day All-cause Mortality	Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal	Through Day 90

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6:CD014945. doi: 10.1002/14651858.CD014945.pub2. Review.
• Maher MC, Soriaga LB, Gupta A, Chen YP, di Iulio J, Ledoux S, Smithey MJ, Cathcart AL, McKusick K, Sun D, Aldinger M, Alexander E, Purcell L, Ding X, Peppercorn A, Austin D, Mogalian E, Yeh WW, Shapiro AE, Corti D, Virgin HW, Pang PS, Telenti A. Antibody therapy reverses biological signatures of COVID-19 progression. Cell Rep Med. 2022 Aug 16;3(8):100721. doi: 10.1016/j.xcrm.2022.100721.
• Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Rodrigues Falci D, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Parra S, Sager JE, Austin D, Peppercorn A, Alexander E, Yeh WW, Brinson C, Aldinger M, Shapiro AE; COMET-ICE Investigators. Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022 Apr 5;327(13):1236-1246. doi: 10.1001/jama.2022.2832.
• Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Hebner CM, Sager J, Mogalian E, Tipple C, Peppercorn A, Alexander E, Pang PS, Free A, Brinson C, Aldinger M, Shapiro AE; COMET-ICE Investigators. Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. N Engl J Med. 2021 Nov 18;385(21):1941-1950. doi: 10.1056/NEJMoa2107934. Epub 2021 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2020
• Primary Completion (Actual): April 8, 2021
• Study Completion (Actual): September 2, 2021

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; coronavirus; coronavirus disease 2019
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: VIR-7831-5001; GSK Study 214367 (Other Identifier: GlaxoSmithKline)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No