VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

Study Overview
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Brief Summary
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This study looks at the safety and effectiveness of VIR-7831 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either VIR-7831 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H2.

Detailed Description
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This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of VIR-7831 in hospitalized patients infected with COVID-19. This is a randomized, blinded, controlled sub-study of VIR-7831 plus current standard of care (SOC) against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo. Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2). An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5. If VIR-7831 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization. This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

Official Title
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A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H2: VIR-7831 (GSK4182136))

Conditions
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COVID-19

Intervention / Treatment
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* Biological: VIR-7831
* Biological: Placebo
* Biological: Remdesivir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refer to the master protocol (NCT04501978) Exclusion Criteria: Refer to the master protocol (NCT04501978) Additional Exclusion Criteria: Pregnant women Nursing mothers In addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on VIR-7831 and 150 on placebo, patients on highflow oxygen or non-invasive ventilation (category 5 of the pulmonary ordinal outcome) will be excluded. These patients may be eligible for the trial if the initial futility assessment is passed by this agent.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIR-7831 plus SOC<br>VIR-7831 500 mg solution (2 vials of 250 mg); administered as a single IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion | Biological: VIR-7831<br>* VIR-7831 is a fully human neutralizing immunoglobulin G (IgG)-1 kappa monoclonal antibody (mAb) derived from antibody S309 from a survivor of SARS-CoV-1.<br>Biological: Remdesivir<br>* Antiviral agent<br>* Other names: Veklury;|
| Placebo Comparator: Placebo plus SOC<br>Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion | Biological: Placebo<br>* Commercially available 0.9% sodium chloride solution<br>Biological: Remdesivir<br>* Antiviral agent<br>* Other names: Veklury;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sustained Recovery | Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90. | Through Day 90 | 
| Number of Participants With an Ordinal Outcome on Day 5 | Ordinal outcome with 7 mutually exclusive categories | Status on Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Died From All Causes | All-cause mortality | Through Day 90 | 
| Number of Participants With a Safety Outcome Through Day 5 | Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5 | Through Day 5 | 
| Number of Participants With a Safety Outcome Through Day 28 | Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28 | Through Day 28 | 
| Number of Participants With a Safety Outcome Through Day 90 | Death, SAE, clinical organ failure, serious infections through Day 90 | Through Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, COVID 19, Coronaviridae Infections, Coronavirus Infections, Virus Diseases, RNA Virus Infections, Nidovirales Infections, SARS-CoV-2, SARS Coronavirus, ACTIV-3, ACTIV3, TICO