Clinical trial NCT04913675: Intramuscular and Intravenous VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19.
Official title: A Phase 3 Randomized, Multi-center, Open Label Study to Assess the Efficacy, Safety, and Tolerability of Monoclonal Antibody VIR-7831 (Sotrovimab) Given Intramuscularly Versus Intravenously for the Treatment of Mild/Moderate Coronavirus Disease 2019 (COVID-19) in High-risk Non-hospitalized Patients; Safety Substudy Assessing the Safety and Tolerability of Single Ascending Dose Monoclonal Antibody VIR-7831
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Covid19
Keywords: SARS-CoV-2
coronavirus disease 2019
COVID-19
early treatment
coronavirus
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2021-06-04
Enrollment: 1065
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression

Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.


Eligibility criteria: Inclusion Criteria:

* Main Study participant must be aged 12 years or older AND at high risk of progression of COVID-19 or \> 55 years old
* Sub-Study participants must be aged 18 years or older at time of consent 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 7 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
* Known hypersensitivity to any constituent present in the investigational product

Primary outcomes:
measure: Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
timeFrame: Up to Day 29
measure: Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8
timeFrame: Up to Day 8
measure: Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8
timeFrame: Up to Day 8
measure: Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8
timeFrame: Up to Day 8
Secondary outcomes:
measure: Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)
timeFrame: Up to Week 12
measure: Main Study: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to Week 36
measure: Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity
timeFrame: Up to Week 36
measure: Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration
timeFrame: Up to Week 36
measure: Main Study: Number of Participants With Any Disease Related Events
timeFrame: Up to Week 36
measure: Safety Sub-study: Number of Participants With Non-SAEs Through Week 12
timeFrame: Up to Week 12
measure: Safety Sub-study: Number of Participants With SAEs Through Week 36
timeFrame: Up to Week 36
measure: Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12
timeFrame: Up to Week 12
measure: Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12
timeFrame: Up to Week 12
measure: Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody
timeFrame: Up to Week 24
measure: Main Study: Titers of Anti-drug Antibodies Against Sotrovimab
timeFrame: Up to Week 24
measure: Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24
timeFrame: Up to Week 24
measure: Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24
timeFrame: Up to Week 24
measure: Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies
timeFrame: Up to Week 24
measure: Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)
timeFrame: Up to Day 29
measure: Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit
timeFrame: Day 8, Day 15, Day 22, and Day 29
measure: Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8
timeFrame: Day 1 to Day 8
measure: Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM
timeFrame: Day 1 to Day 8
measure: Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8
timeFrame: Baseline (Day 1) and at Day 8
measure: Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8
timeFrame: At Day 8
measure: Main Study: Serum Concentration of Sotrovimab After Intravenous Administration
timeFrame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
measure: Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration
timeFrame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
measure: Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose
measure: Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
measure: Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)
timeFrame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Other outcomes:
Locations:
city: Anniston
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: Rolling Hills Estates
country: United States
facility: Investigative Site
state: California
city: Bradenton
country: United States
facility: Investigative Site
state: Florida
city: Doral
country: United States
facility: Investigative Site
state: Florida
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: Hialeah
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: 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: North Miami Beach
country: United States
facility: Investigative Site
state: Florida
city: Ormond Beach
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 Sites
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: Idaho Falls
country: United States
facility: Investigative Site
state: Idaho
city: Mishawaka
country: United States
facility: Investigative Site
state: Indiana
city: Sterling Heights
country: United States
facility: Investigative Site
state: Michigan
city: Las Vegas
country: United States
facility: Investigative Site
state: Nevada
city: Bronx
country: United States
facility: Investigative Site
state: New York
city: High Point
country: United States
facility: Investigative Site
state: North Carolina
city: Mount Airy
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: Baytown
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: Laredo
country: United States
facility: Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Investigative Site
state: Texas
city: Pharr
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: Limoges
country: France
facility: Investigative Site
state: Haute-Vienna
city: Kyiv
country: Ukraine
facility: Investigative Site
Study officials:
References:
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.