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) (REDPINE)

• ClinicalTrials.gov Identifier: NCT04745351
• Recruitment Status: Terminated
• First Posted: February 9, 2021
• Results First Posted: May 12, 2023
• Last Update Posted: May 12, 2023
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 8, 2021
• First Posted Date: February 9, 2021
• Results First Submitted Date: April 18, 2023
• Results First Posted Date: May 12, 2023
• Last Update Posted Date: May 12, 2023
• Actual Study Start Date: March 31, 2021
• Actual Primary Completion Date: April 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2023)

Percentage of Participants With All-cause Death or Invasive Mechanical Ventilation (IMV) Through Day 29 [ Time Frame: First dose date up to Day 29 ]

This is the combined outcome measure reporting the percentage of participants with all-cause death or IMV through Day 29. The reported percentage was from the Kaplan-Meier estimate.

Original 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.

Current Secondary Outcome Measures (submitted: April 18, 2023)

• All-cause Mortality Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  The reported percentage was from the Kaplan-Meier estimate.
• Percentage of Participants With Initiation of IMV Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  The reported percentage was the cumulative-incidence estimate.
• Time to Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) by Day 29 [ 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 with a baseline score ≥ 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. Cumulative incidence was reported.
• Time to Recovery Independent of Further Worsening by Day 29 [ 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 with a baseline score ≥ 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. Cumulative incidence was reported.
• Percentage of Participants Within Each Clinical Status Category as 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 was recorded. The 8-point 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 IMV or ECMO; and 8. Death. Higher scores indicate worse clinical status.
• Percentage of Participants Within Each Clinical Status Category as 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 was recorded. The 8-point 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 IMV or ECMO; and 8. Death. Higher scores indicate worse clinical status.
• Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Baseline) Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  The number of RRT free days were calculated as the number of full days from Day 1 to Day 29 on which the participant was alive and did not receive RRT.
• Percentage of Participants With Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  Recovery is defined as the first day on which the participant with a baseline score >= 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale including: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on IMV or ECMO; 8) Death.
• Percentage of Participants With Recovery Independent of Further Worsening Through Day 29 [ Time Frame: First dose date up to Day 29 ]
  Recovery is defined as the first day on which the participant with a baseline score >= 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale including: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on IMV or ECMO; 8) Death.
• Percentage of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: First dose date up to last dose date (Maximum: 5 days) plus 30 days ]
  An SAE was defined as an event that, at any dose, results in the following: Death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, a medically important event or reaction which may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes constituting SAEs.
• Percentage of Participants Who Permanently Discontinued Investigational Drug Due to Adverse Events (AEs) [ Time Frame: First dose date up to last dose date (Maximum: 5 days) ]
  An AE is any untoward medical occurrence in a clinical study participant administered an investigational drug, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of an investigational drug, whether or not the AE is considered related to the investigational drug.

Original 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 ]

• 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 matching placebo on Day 1 followed by RDV matching placebo from Day 2 up to Day 5.
  Interventions:

  • Drug: RDV Placebo
  • Drug: Standard of Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 10, 2022): 249
• Original Estimated Enrollment (submitted: February 8, 2021): 1116
• Actual Study Completion Date: May 24, 2022
• Actual Primary Completion Date: April 20, 2022 (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

• Have either:

  • a) Severely reduced kidney function (estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m^2), including people with end-stage kidney disease (ESKD) requiring chronic dialysis
  • b) Ongoing acute kidney injury (AKI): defined as a 50% increase in serum creatinine (SCr) within a 48-hour period that is sustained (ie, requires confirmatory SCr) for ≥ 6 hours despite supportive care
• 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, extracorporeal membrane oxygenation (ECMO), or renal replacement therapy (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 information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Portugal, South Africa, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04745351
• Other Study ID Numbers: GS-US-540-5912; 2020-005416-22 ( EudraCT Number ); DOH-27-012022-4779 ( Registry Identifier: South African Clinical Trials Register )
• 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.gileadclinicaltrials.com/transparency-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.gileadclinicaltrials.com/transparency-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: April 2023