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

Phase 2

Completed

Conditions: Covid19

Interventions: Biological: VIR-7831 (sotrovimab)
Drug: Placebo

Registration Number: NCT04545060

Lead Sponsor: Vir Biotechnology, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1057

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VIR-7831 (Sotrovimab)	VIR-7831 (sotrovimab)	Participants received 500 mg sotrovimab administered intravenously (IV)
Placebo	Placebo	Participants received placebo administered intravenously (IV)

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Had Progression of COVID-19 Through Day 29	Through Day 29	COVID-19 progression defined as hospitalization \>24 hours or death

Secondary Outcome Measures

Name	Time	Method
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
Number of Participants With Adverse Events (AEs)	Up to 24 weeks
Number of Participants With Cardiac Events of Special Interest	Up to 24 weeks
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
Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions	Up to 24 weeks
Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab	Up to 24 Weeks	Titers defined as the reciprocal of the highest dilution of the sample (including minimum required dilution) that yields a positive result.
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
Mean Change in FLU PRO Plus Total Score (AUC)	Through Day 7	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.
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
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 With Serum Anti-drug Antibody (ADA) to Sotrovimab	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
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
Number of Participants Who Had Progression of COVID-19	Through Day 29	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
Time to Symptom Alleviation Using FLU-PRO Plus	Through Day 21	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.
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
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
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	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.
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	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.
90-day All-cause Mortality	Through Day 90	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
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
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 15	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.
29-day All-cause Mortality	Through Day 29	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
60-day All-cause Mortality	Through Day 60	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
Number of Participants With Serious Adverse Events (SAEs)	Up to 24 weeks