Clinical trial NCT04545060: VIR-7831 for the Early Treatment of COVID-19 in Outpatients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: SARS-CoV-2
coronavirus
coronavirus disease 2019
COVID-19
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2020-09-10
Enrollment: 1057
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Had Progression of COVID-19 Through Day 29
timeFrame: Through Day 29
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 24 weeks
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 24 weeks
measure: Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions
timeFrame: Up to 24 weeks
measure: Number of Participants With Cardiac Events of Special Interest
timeFrame: Up to 24 weeks
measure: Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab
timeFrame: Up to 24 weeks
measure: Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab
timeFrame: Up to 24 Weeks
measure: Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Concentration at the Last Quantifiable Time Point (Clast) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Time to Reach the Maximum Concentration (Tmax) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUCinf) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: 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
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Percentage of AUCinf Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Apparent Volume of Distribution During the Elimination Phase (Vz) of VIR-7831 Following IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 Following IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Clearance (CL) of VIR-7831 After IV Administration
timeFrame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
measure: Number of Participants Who Had Progression of COVID-19
timeFrame: Through Day 29
measure: Mean Change in FLU PRO Plus Total Score (AUC)
timeFrame: Through Day 7
measure: Time to Symptom Alleviation Using FLU-PRO Plus
timeFrame: Through Day 21
measure: Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8
timeFrame: Baseline and Day 8
measure: 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
timeFrame: Through Day 8
measure: 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
timeFrame: Through Day 15
measure: 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
timeFrame: Through Day 22
measure: 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
timeFrame: Through Day 29
measure: 29-day All-cause Mortality
timeFrame: Through Day 29
measure: 60-day All-cause Mortality
timeFrame: Through Day 60
measure: 90-day All-cause Mortality
timeFrame: Through Day 90
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Investigative Site
state: Alabama
city: Cullman
country: United States
facility: Investigative Site
state: Alabama
city: Mesa
country: United States
facility: Investigative Site
state: Arizona
city: Tucson
country: United States
facility: Investigative Site
state: Arizona
city: Los Angeles
country: United States
facility: Investigative Site
state: California
city: Los Angeles
country: United States
facility: Investigative Site
state: California
city: Northridge
country: United States
facility: Investigative Site
state: California
city: Oxnard
country: United States
facility: Investigative Site
state: California
city: Rolling Hills Estates
country: United States
facility: Investigative Site
state: California
city: Sacramento
country: United States
facility: Investigative Site
state: California
city: Doral
country: United States
facility: Investigative Site
state: Florida
city: Gainesville
country: United States
facility: Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Investigative Site
state: Florida
city: Miami
country: United States
facility: Investigative Site
state: Florida
city: Miami
country: United States
facility: Investigative Site
state: Florida
city: Miami
country: United States
facility: Investigative Site
state: Florida
city: Miami
country: United States
facility: Investigative Site
state: Florida
city: Miami
country: United States
facility: Investigative Site
state: Florida
city: Miramar
country: United States
facility: Investigative Site
state: Florida
city: North Miami
country: United States
facility: Investigative Site
state: Florida
city: Palmetto Bay
country: United States
facility: Investigative Site
state: Florida
city: Pembroke Pines
country: United States
facility: Investigative Site
state: Florida
city: Pompano Beach
country: United States
facility: Investigative Site
state: Florida
city: Tampa
country: United States
facility: Investigative Site
state: Florida
city: Tampa
country: United States
facility: Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Investigative Site
state: Georgia
city: Atlanta
country: United States
facility: Investigative Site
state: Georgia
city: Decatur
country: United States
facility: Investigative Site
state: Georgia
city: Stockbridge
country: United States
facility: Investigative Site
state: Georgia
city: Idaho Falls
country: United States
facility: Investigative Site
state: Idaho
city: Mishawaka
country: United States
facility: Investigative Site
state: Indiana
city: Lake Charles
country: United States
facility: Investigative Site
state: Louisiana
city: Marrero
country: United States
facility: Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Investigative Site
state: Maryland
city: Caro
country: United States
facility: Investigative Site
state: Michigan
city: Hazelwood
country: United States
facility: Investigative Site
state: Missouri
city: Las Vegas
country: United States
facility: Investigative Site
state: Nevada
city: Las Vegas
country: United States
facility: Investigative Site
state: Nevada
city: Santa Fe
country: United States
facility: Investigative Site
state: New Mexico
city: Bronx
country: United States
facility: Investigative Site
state: New York
city: Asheboro
country: United States
facility: Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Investigative Site
state: North Carolina
city: Columbus
country: United States
facility: Investigative Site
state: Ohio
city: Smithfield
country: United States
facility: Investigative Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Investigative Site
state: Texas
city: Baytown
country: United States
facility: Investigative Site
state: Texas
city: Beaumont
country: United States
facility: Investigative Site
state: Texas
city: Dallas
country: United States
facility: Investigative Site
state: Texas
city: Denton
country: United States
facility: Investigative Site
state: Texas
city: El Paso
country: United States
facility: Investigative Site
state: Texas
city: Forney
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: Humble
country: United States
facility: Investigative Site
state: Texas
city: Laredo
country: United States
facility: Investigative Site
state: Texas
city: McAllen
country: United States
facility: Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Investigative Site
state: Texas
city: Sugar Land
country: United States
facility: Investigative Site
state: Texas
city: Kirkland
country: United States
facility: Investigative Site
state: Washington
city: Seattle
country: United States
facility: Investigative Site
state: Washington
city: Vienna
country: Austria
facility: Investigative Site
city: Vienna
country: Austria
facility: Investigative Site
city: Belo Horizonte
country: Brazil
facility: Investigative Site
state: Minas Gerais
city: Maringá
country: Brazil
facility: Investigative Site
state: Parana
city: Natal
country: Brazil
facility: Investigative Site
state: Rio Grande Do Norte
city: Passo Fundo
country: Brazil
facility: Investigative Site
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Investigative Site
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Investigative Site
state: Rio Grande Do Sul
city: Chapecó
country: Brazil
facility: Investigative Site
state: Santa Catarina
city: Santo André
country: Brazil
facility: Investigative Site
state: Sao Paulo
city: Vila Assuncao
country: Brazil
facility: Investigative Site
state: Sao Paulo
city: Campinas
country: Brazil
facility: Investigative Site
state: São Paulo
city: Sarnia
country: Canada
facility: Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Investigative Site
state: Ontario
city: Québec
country: Canada
facility: Investigative Site
state: Quebec
city: Bellavista
country: Peru
facility: Investigative Site
state: Callao
city: El Agustino
country: Peru
facility: Investigative Site
state: Lima
city: Huaral
country: Peru
facility: Investigative Site
state: Lima
city: San Isidro
country: Peru
facility: Investigative Site
state: Lima
city: Bella Vista
country: Peru
facility: Investigative Site
city: Lima
country: Peru
facility: Investigative Site
city: Centelles
country: Spain
facility: Investigative Site
state: Barcelona
city: Terrassa
country: Spain
facility: Investigative Site
state: Barcelona
city: Albacete
country: Spain
facility: Investigative Site
city: Girona
country: Spain
facility: Investigative Site
city: Granada
country: Spain
facility: Investigative Site
city: Vigo
country: Spain
facility: Investigative Site
city: Belfast
country: United Kingdom
facility: Investigative Site
Study officials:
References:
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 therapy reverses biological signatures of COVID-19 progression. Cell Rep Med. 2022 Aug 16;3(8):100721. doi: 10.1016/j.xcrm.2022.100721.
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. 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.
citation: 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.
citation: 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(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
citation: 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.