Study to Evaluate the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for Coronavirus Disease 2019 (COVID-19)

• ClinicalTrials.gov Identifier: NCT04745351
• Recruitment Status: Recruiting
• First Posted: February 9, 2021
• Last Update Posted: March 23, 2021
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 8, 2021
• First Posted Date: February 9, 2021
• Last Update Posted Date: March 23, 2021
• Estimated Study Start Date: March 2021
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2021)

Composite of All-Cause Mortality or Invasive Mechanical Ventilation (IMV) Through Day 29 [ Time Frame: First dose date up to Day 29 ]

The composite of all-cause mortality or IMV is the combined endpoint of the percentage of participants who die or initiate on IMV through Day 29.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 8, 2021)

• All-Cause Mortality Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  The percentage of participants who die through Day 29 will be assessed.
• Invasive Mechanical Ventilation Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  The percentage of participants who initiate on IMV through Day 29 will be assessed.
• Time to Recovery [ Time Frame: First dose date up to Day 29 ]
  Time to recovery is the time from first dose to recovery. Recovery is defined as the first day on which the participant satisfies one of the following three categories from the 8-point ordinal scale: 1) Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration).
• Clinical Status Assessed by an 8-Point Ordinal Scale on Day 15 [ Time Frame: Day 15 ]
  Clinical status is derived from death, hospital discharge, and the ordinal scale. Each day, the worst (highest) score from the previous day will be recorded. The Ordinal scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19-specific medical care (other than per-protocol RDV administration); 5. Hospitalized, supplemental oxygen; 6. Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8. Death. Higher scores indicate worst clinical status.
• Clinical Status Assessed by an 8-Point Ordinal Scale on Day 29 [ Time Frame: Day 29 ]
  Clinical status is derived from death, hospital discharge, and the ordinal scale. Each day, the worst (highest) score from the previous day will be recorded. The Ordinal scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19-specific medical care (other than per-protocol RDV administration); 5. Hospitalized, supplemental oxygen; 6. Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; and 8. Death. Higher scores indicate worst clinical status.
• Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Randomization) Through Day 29 [ Time Frame: First dose date up to Day 29 ]
• Recovery Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  Recovery is defined as the participant satisfying one of the following three categories from the 8-point ordinal scale: 1) Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration).
• Percentage of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: First dose date up to last dose date (Maximum: Day 5) plus 30 days ]
• Percentage of Participants who Permanently Discontinue Investigational Drug due to Adverse Events (AEs) [ Time Frame: First dose date up to last dose date (Maximum: Day 5) plus 30 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for Coronavirus Disease 2019 (COVID-19)
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for COVID-19
• Brief Summary: The primary objective of this study is to evaluate whether remdesivir (RDV, GS-5734™) reduces the composite risk of death or invasive mechanical ventilation (IMV) through Day 29 in participants with severely reduced kidney function who are hospitalized for coronavirus disease 2019 (COVID-19).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Remdesivir
  Administered as Intravenous (IV) infusion once daily
  Other Names:

  • GS-5734™
  • Veklury®
• Drug: RDV Placebo
  Administered as IV saline once daily
• Drug: Standard of Care
  Standard of Care Treatment for COVID-19 Infection

Study Arms

• Experimental: Remdesivir (RDV)
  Participants will receive continued Standard of Care (SOC) therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg from Day 2 up to Day 5.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Placebo Comparator: Placebo
  Participants will receive continued SOC therapy together with RDV placebo on Day 1 followed by RDV placebo from Day 2 up to Day 5.
  Interventions:

  • Drug: RDV Placebo
  • Drug: Standard of Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 8, 2021): 1116
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive as determined by Polymerase Chain Reaction (PCR) or other commercially available or public health assay (eg, Nucleic Acid Amplification Test [NAAT] and antigen tests) in any respiratory specimen
• Hospitalized for COVID-19
• Weighing at least 40 kilograms (kg)
• Oxygen (O2) saturation ≤ 94% on room air or requiring O2 supplement or Radiographic evidence of pulmonary infiltrates for COVID-19
• Severely reduced kidney function (estimated Glomerular Filtration Rate [eGFR] < 30 milliliters per minute per 1.73 square meters [mL/min/1.73 m^2]), including people with ESKD requiring chronic dialysis
• The interval between COVID-19 symptoms onset and randomization is no more than 10 days

Key Exclusion Criteria:

• Received any investigational drug, RDV, or other antiviral treatment for COVID-19
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal
• Invasive mechanical ventilation, noninvasive mechanical ventilation, ECMO, or RRT for acute kidney injury (AKI)
• Positive serum pregnancy test at screening for women of childbearing potential or currently breastfeeding
• Known hypersensitivity to the study drug, metabolites, or formulation sulfobutylether-beta-cyclodextrin (SBECD)

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: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04745351
• Other Study ID Numbers: GS-US-540-5912; 2020-005416-22 ( EudraCT Number )
• 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: No

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

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