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

• ClinicalTrials.gov Identifier: NCT04292730
• Recruitment Status: Completed
• First Posted: March 3, 2020
• Results First Posted: January 26, 2021
• Last Update Posted: January 26, 2021
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 28, 2020
• First Posted Date: March 3, 2020
• Results First Submitted Date: December 15, 2020
• Results First Posted Date: January 26, 2021
• Last Update Posted Date: January 26, 2021
• Actual Study Start Date: March 15, 2020
• Actual Primary Completion Date: April 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2020)

Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: February 28, 2020): Proportion of Participants Discharged by Day 14 [ Time Frame: First dose date or randomization date up to 14 days ]

Current Secondary Outcome Measures (submitted: December 15, 2020)

Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to last dose date (maximum: 10 days) plus 30 days ]

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.

• Original Secondary Outcome Measures (submitted: February 28, 2020): Proportion of Participants With Treatment Emergent Adverse Events Leading to Study Drug Discontinuation [ Time Frame: First dose date up to 10 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Remdesivir
  Administered as an intravenous infusion
  Other Names:

  • GS-5734™
  • Veklury®
• Drug: Standard of Care
  Standard of Care Treatment for COVID-19 Infection

Study Arms

• Experimental: Part A: Remdesivir (RDV), 5 Days
  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.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Experimental: Part A: Remdesivir, 10 Days
  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.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Active Comparator: Part A: SOC Therapy
  Participants will receive continued standard of care therapy.
  Intervention: Drug: Standard of Care
• Experimental: Part B: Extension Treatment, Remdesivir 10 Days
  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.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care

Publications *

• Spinner CD, Gottlieb RL, Criner GJ, Arribas Lopez JR, Cattelan AM, Soriano Viladomiu A, Ogbuagu O, Malhotra P, Mullane KM, Castagna A, Chai LYA, Roestenberg M, Tsang OTY, Bernasconi E, Le Turnier P, Chang SC, SenGupta D, Hyland RH, Osinusi AO, Cao H, Blair C, Wang H, Gaggar A, Brainard DM, McPhail MJ, Bhagani S, Ahn MY, Sanyal AJ, Huhn G, Marty FM; GS-US-540-5774 Investigators. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020 Sep 15;324(11):1048-1057. doi: 10.1001/jama.2020.16349.
• Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 23, 2020): 1113
• Original Estimated Enrollment (submitted: February 28, 2020): 600
• Actual Study Completion Date: June 26, 2020
• Actual Primary Completion Date: April 29, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Iran, Islamic Republic of

Administrative Information

• NCT Number: NCT04292730
• Other Study ID Numbers: GS-US-540-5774; 2020-000842-32 ( EudraCT Number ); ISRCTN85762140 ( Other Identifier: ISRCTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: January 2021