Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale on Day 11.

Official Title
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A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate COVID-19 Compared to Standard of Care Treatment

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Remdesivir
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent prior to performing study procedures (participants ≥ 18 years of age) or assent (participants ≥ 12 and < 18 years of age) prior to performing study procedures. For participants ≥ 12 and < 18 years of age, a parent or legal guardian willing and able to provide written informed consent prior to performing study procedures Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization Currently hospitalized and requiring medical care for COVID-19 Peripheral capillary oxygen saturation (SpO2) > 94% on room air at screening Radiographic evidence of pulmonary infiltrates Key Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19 Concurrent treatment or planned concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 Requiring mechanical ventilation at screening Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN) Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976} and Schwartz Formula for participants < 18 years of age Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Remdesivir (RDV), 5 Days<br>Participants will receive continued standard of care (SOC) therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5. | Drug: Remdesivir<br>* Administered as an intravenous infusion<br>* Other names: Veklury®;Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|
| Experimental: Part A: Remdesivir, 10 Days<br>Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10. | Drug: Remdesivir<br>* Administered as an intravenous infusion<br>* Other names: Veklury®;Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|
| Active Comparator: Part A: SOC Therapy<br>Participants will receive continued standard of care therapy. | Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|
| Experimental: Part B: Extension Treatment, Remdesivir 10 Days<br>Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10. | Drug: Remdesivir<br>* Administered as an intravenous infusion<br>* Other names: Veklury®;Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Clinical status was derived from death, hospital discharge, and ordinal scale as follows: score of 1 was used for all days on or after the date of death; score of 7 was used for all days on or after discharged alive date; last available assessment for missing value. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol remdesivir administration; 7. Not hospitalized. The odds ratio represents the odds of improvement in the ordinal scale for a RDV group relative to the SOC group. | Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | TEAEs were defined as the following: any AE with an onset date on or after the study treatment start date and no later than 30 days after permanent discontinuation of study treatment and/or any AE leading to premature discontinuation of study treatment. For participants randomized to the SOC group, all AEs reported on or after the protocol-specified Day 1 visit were considered as treatment emergent. | First dose date up to last dose date (maximum: 10 days) plus 30 days |