Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe Coronavirus Disease (COVID-19)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.

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 Severe COVID-19

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, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (age ≥ 18), or willing and able to provide assent (age ≥ 12 to < 18, where locally and nationally approved) prior to performing study procedures Aged ≥ 18 years (at all sites), or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC)) Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization Currently hospitalized Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening Key Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19 Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study drug dosing Evidence of multiorgan failure Mechanically ventilated [including veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)] ≥ 5 days, or any duration of veno-arterial (V-A) ECMO. 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 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>|
| Experimental: Part B: Remdesivir, 10 Days (Extension)<br>Part B (Extension) will enroll participants after enrollment to Part A is complete. Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10. | 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>|
| Experimental: Part B: Remdesivir 10 days (Mechanically Ventilated)<br>Participants on mechanical ventilation will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10 | 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 14 | Clinical status was derived from death, hospital discharge, and the 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 assessment carried forward for any missing values.The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or 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 (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 the Remdesivir for 10 days group vs the Remdesivir for 5 days group. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study treatment start date and no later than 30 days after the permanent discontinuation of the study treatment and/or the AEs that led to premature discontinuation of study treatment. | First dose date up to last dose date (maximum: 10 days) plus 30 days |