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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Covid19

Intervention / Treatment
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* Biological: VIR-7831 (sotrovimab)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, coronavirus, coronavirus disease 2019, COVID-19