VIR-7831 for the Early Treatment of COVID-19 in Outpatients

Covid19 Clinical Trial

— COMET-ICE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04545060
• Other study ID #: VIR-7831-5001
• Secondary ID: GSK Study 214367
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 27, 2020
• Est. completion date: September 2, 2021

Study information

• Verified date: October 2022
• Source: Vir Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1057
• Est. completion date: September 2, 2021
• Est. primary completion date: April 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• VIR-7831 (sotrovimab)
VIR-7831 (sotrovimab) given by intravenous infusion (single dose)

Drug:
• Placebo
Sterile normal saline (0.9% NaCl) given by intravenous infusion (single dose)

Locations

Country	Name	City	State
Austria	Investigative Site	Vienna
Austria	Investigative Site	Vienna
Brazil	Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Investigative Site	Campinas	São Paulo
Brazil	Investigative Site	Chapecó	Santa Catarina
Brazil	Investigative Site	Maringá	Parana
Brazil	Investigative Site	Natal	Rio Grande Do Norte
Brazil	Investigative Site	Passo Fundo	Rio Grande Do Sul
Brazil	Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Investigative Site	Santo André	Sao Paulo
Brazil	Investigative Site	Vila Assuncao	Sao Paulo
Canada	Investigative Site	Québec	Quebec
Canada	Investigative Site	Sarnia	Ontario
Canada	Investigative Site	Toronto	Ontario
Peru	Investigative Site	Bella Vista
Peru	Investigative Site	Bellavista	Callao
Peru	Investigative Site	El Agustino	Lima
Peru	Investigative Site	Huaral	Lima
Peru	Investigative Site	Lima
Peru	Investigative Site	San Isidro	Lima
Spain	Investigative Site	Albacete
Spain	Investigative Site	Centelles	Barcelona
Spain	Investigative Site	Girona
Spain	Investigative Site	Granada
Spain	Investigative Site	Terrassa	Barcelona
Spain	Investigative Site	Vigo
United Kingdom	Investigative Site	Belfast
United States	Investigative Site	Anniston	Alabama
United States	Investigative Site	Asheboro	North Carolina
United States	Investigative Site	Atlanta	Georgia
United States	Investigative Site	Atlanta	Georgia
United States	Investigative Site	Austin	Texas
United States	Investigative Site	Baltimore	Maryland
United States	Investigative Site	Baytown	Texas
United States	Investigative Site	Beaumont	Texas
United States	Investigative Site	Bronx	New York
United States	Investigative Site	Caro	Michigan
United States	Investigative Site	Charlotte	North Carolina
United States	Investigative Site	Chattanooga	Tennessee
United States	Investigative Site	Columbus	Ohio
United States	Investigative Site	Cullman	Alabama
United States	Investigative Site	Dallas	Texas
United States	Investigative Site	Decatur	Georgia
United States	Investigative Site	Denton	Texas
United States	Investigative Site	Doral	Florida
United States	Investigative Site	El Paso	Texas
United States	Investigative Site	Forney	Texas
United States	Investigative Site	Gainesville	Florida
United States	Investigative Site	Hazelwood	Missouri
United States	Investigative Site	Hialeah	Florida
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Humble	Texas
United States	Investigative Site	Idaho Falls	Idaho
United States	Investigative Site	Kirkland	Washington
United States	Investigative Site	Lake Charles	Louisiana
United States	Investigative Site	Laredo	Texas
United States	Investigative Site	Las Vegas	Nevada
United States	Investigative Site	Las Vegas	Nevada
United States	Investigative Site	Los Angeles	California
United States	Investigative Site	Los Angeles	California
United States	Investigative Site	Marrero	Louisiana
United States	Investigative Site	McAllen	Texas
United States	Investigative Site	Mesa	Arizona
United States	Investigative Site	Mesquite	Texas
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miramar	Florida
United States	Investigative Site	Mishawaka	Indiana
United States	Investigative Site	North Miami	Florida
United States	Investigative Site	Northridge	California
United States	Investigative Site	Oxnard	California
United States	Investigative Site	Palmetto Bay	Florida
United States	Investigative Site	Pembroke Pines	Florida
United States	Investigative Site	Pompano Beach	Florida
United States	Investigative Site	Rolling Hills Estates	California
United States	Investigative Site	Sacramento	California
United States	Investigative Site	Santa Fe	New Mexico
United States	Investigative Site	Seattle	Washington
United States	Investigative Site	Smithfield	Pennsylvania
United States	Investigative Site	Stockbridge	Georgia
United States	Investigative Site	Sugar Land	Texas
United States	Investigative Site	Tampa	Florida
United States	Investigative Site	Tampa	Florida
United States	Investigative Site	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Vir Biotechnology, Inc.	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Canada,  Peru,  Spain,  United Kingdom, 

References & Publications (3)

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 Inv — View Citation

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. E — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Adverse Events (AEs)		Up to 24 weeks
Secondary	Number of Participants With Serious Adverse Events (SAEs)		Up to 24 weeks
Secondary	Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions		Up to 24 weeks
Secondary	Number of Participants With Cardiac Events of Special Interest		Up to 24 weeks
Secondary	Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab		Up to 24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8		Baseline and Day 8
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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