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).
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)
Categories
Completion Date
Completion Date Type
Actual
Conditions
COVID-19
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
* 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
Inclusion Criteria
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
Inclusion/
* 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
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT04745351
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-540-5912
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With All-cause Death or Invasive Mechanical Ventilation (IMV) Through Day 29
Outcome Time Frame
First dose date up to Day 29
Secondary Ids
Secondary Id
2020-005416-22
Secondary Id
DOH-27-012022-4779
Secondary Outcomes
Outcome Description
The reported percentage was from the Kaplan-Meier estimate.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
All-cause Mortality Through Day 29
Outcome Description
The reported percentage was the cumulative-incidence estimate.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Percentage of Participants With Initiation of IMV Through Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Time to Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) by Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Time to Recovery Independent of Further Worsening by Day 29
Outcome Description
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.
Outcome Time Frame
Day 15
Outcome Measure
Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on Day 15
Outcome Description
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.
Outcome Time Frame
Day 29
Outcome Measure
Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Baseline) Through Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Percentage of Participants With Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) Through Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to Day 29
Outcome Measure
Percentage of Participants With Recovery Independent of Further Worsening Through Day 29
Outcome Description
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.
Outcome Time Frame
First dose date up to last dose date (Maximum: 5 days) plus 30 days
Outcome Measure
Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Outcome Description
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.
Outcome Time Frame
First dose date up to last dose date (Maximum: 5 days)
Outcome Measure
Percentage of Participants Who Permanently Discontinued Investigational Drug Due to Adverse Events (AEs)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Barry Zingman
Investigator Email
bzingman@montefiore.org
Investigator Phone
718-920-2647