Brief Summary
The goals of this clinical study are to learn more about the study drug, remdesivir, and how safe it is in participants less than 18 years old with coronavirus disease 2019 (COVID-19).
Brief Title
Study of Remdesivir in Participants Below 18 Years Old With COVID-19
Detailed Description
Pediatric participants will be enrolled as follows:
Pediatric participants ≥ 28 days to \< 18 years old:
* Cohort 1: ≥ 12 years to \< 18 years and weight ≥ 40 kg
* Cohort 2: ≥ 28 days to \< 18 years and weight ≥ 20 kg to \< 40 kg
* Cohort 3: ≥ 28 days to \< 18 years and weight ≥ 12 kg to \< 20 kg
* Cohort 4: ≥ 28 days to \< 18 years and weight ≥ 3 kg to \< 12 kg
* Cohort 8: \< 12 years and weight ≥ 40 kg
Term neonatal participants 0 days to \< 28 days old:
* Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight ≥ 2.5 kg
Preterm neonates and infants 0 days to \< 56 days old:
* Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight ≥ 1.5 kg
Pediatric participants ≥ 28 days to \< 18 years old:
* Cohort 1: ≥ 12 years to \< 18 years and weight ≥ 40 kg
* Cohort 2: ≥ 28 days to \< 18 years and weight ≥ 20 kg to \< 40 kg
* Cohort 3: ≥ 28 days to \< 18 years and weight ≥ 12 kg to \< 20 kg
* Cohort 4: ≥ 28 days to \< 18 years and weight ≥ 3 kg to \< 12 kg
* Cohort 8: \< 12 years and weight ≥ 40 kg
Term neonatal participants 0 days to \< 28 days old:
* Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight ≥ 2.5 kg
Preterm neonates and infants 0 days to \< 56 days old:
* Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight ≥ 1.5 kg
Categories
Completion Date
Completion Date Type
Actual
Conditions
COVID-19
Eligibility Criteria
Key Inclusion Criteria:
* Aged \< 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board (IRB) or independent ethics committee (IEC)).
* a) Cohort 1: ≥ 12 years to \< 18 years of age and weight at screening ≥ 40 kg
* b) Cohorts 2-4: ≥ 28 days to \< 18 years of age and weight at screening ≥ 3 kg and \< 40 kg
* c) Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* d) Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight of ≥ 2.5 kg
* e) Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
* f) Cohort 8: \< 12 years of age and weight at screening ≥ 40 kg
* Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR).
* Hospitalized and requiring medical care for coronavirus disease 2019 (COVID-19).
Key Exclusion Criteria:
* Concurrent treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 \< 24 hours prior to study drug dosing.
* Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN).
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\^2 using Schwartz formula for individuals ≥ 1 year of age.
* Creatinine above protocol specified thresholds for \< 1 year of age.
* Positive pregnancy test at Screening only for female of child bearing potential. Note: If female participants who become pregnant during the study or are discovered to be pregnant after receiving at least one dose may continue study drug, after discussion with the investigator.
* On renal replacement therapies (intermittent hemodialysis (iHD), peritoneal dialysis (PD), continuous renal replacement therapy (CRRT)).
Note: Other protocol defined Inclusion/Exclusion criteria may apply
* Aged \< 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board (IRB) or independent ethics committee (IEC)).
* a) Cohort 1: ≥ 12 years to \< 18 years of age and weight at screening ≥ 40 kg
* b) Cohorts 2-4: ≥ 28 days to \< 18 years of age and weight at screening ≥ 3 kg and \< 40 kg
* c) Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* d) Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight of ≥ 2.5 kg
* e) Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
* f) Cohort 8: \< 12 years of age and weight at screening ≥ 40 kg
* Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR).
* Hospitalized and requiring medical care for coronavirus disease 2019 (COVID-19).
Key Exclusion Criteria:
* Concurrent treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 \< 24 hours prior to study drug dosing.
* Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN).
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\^2 using Schwartz formula for individuals ≥ 1 year of age.
* Creatinine above protocol specified thresholds for \< 1 year of age.
* Positive pregnancy test at Screening only for female of child bearing potential. Note: If female participants who become pregnant during the study or are discovered to be pregnant after receiving at least one dose may continue study drug, after discussion with the investigator.
* On renal replacement therapies (intermittent hemodialysis (iHD), peritoneal dialysis (PD), continuous renal replacement therapy (CRRT)).
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Inclusion Criteria
Inclusion Criteria:
* Aged \< 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board (IRB) or independent ethics committee (IEC)).
* a) Cohort 1: ≥ 12 years to \< 18 years of age and weight at screening ≥ 40 kg
* b) Cohorts 2-4: ≥ 28 days to \< 18 years of age and weight at screening ≥ 3 kg and \< 40 kg
* c) Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* d) Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight of ≥ 2.5 kg
* e) Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
* f) Cohort 8: \< 12 years of age and weight at screening ≥ 40 kg
* Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR).
* Hospitalized and requiring medical care for coronavirus disease 2019 (COVID-19).
Inclusion/
* Aged \< 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board (IRB) or independent ethics committee (IEC)).
* a) Cohort 1: ≥ 12 years to \< 18 years of age and weight at screening ≥ 40 kg
* b) Cohorts 2-4: ≥ 28 days to \< 18 years of age and weight at screening ≥ 3 kg and \< 40 kg
* c) Cohort 5: ≥ 14 days to \< 28 days of age, gestational age \> 37 weeks and weight at screening ≥ 2.5 kg
* d) Cohort 6: 0 days to \< 14 days of age, gestational age \> 37 weeks and birth weight of ≥ 2.5 kg
* e) Cohort 7: 0 days to \< 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
* f) Cohort 8: \< 12 years of age and weight at screening ≥ 40 kg
* Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR).
* Hospitalized and requiring medical care for coronavirus disease 2019 (COVID-19).
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
18 Years
NCT Id
NCT04431453
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-540-5823
Overall Status
Completed
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2/3 Single-Arm, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Remdesivir (GS-5734™) in Participants From Birth to < 18 Years of Age With COVID-19
Primary Outcomes
Outcome Description
TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.
Outcome Measure
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Outcome Time Frame
From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Description
Treatment-emergent graded laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any time post baseline up to and including the date of last dose of study drug plus 30 days. The laboratory abnormalities were graded using division of allergy and infectious diseases (DAIDS) scale. DAIDS scale is used to grade the severity of adult and pediatric unwanted medical events. Grade 1: mild event, Grade 2: moderate event, Grade: serious event, Grade 4: potentially life-threatening event.
Outcome Measure
Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities
Outcome Time Frame
From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Description
Cmax is defined as maximum plasma concentration of drug. Plasma concentrations were drawn as follows: (1) for Cohorts 1-4 and 8 on Day 2 and Day 3 with Day 5 as optional; (2) for Cohorts 5-7 on Day 2 or Day 3.
Outcome Measure
Pharmacokinetic (PK) Parameter: Cmax of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State
Outcome Time Frame
Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hours
Outcome Description
AUCtau is defined as area under the concentration versus time curve over the dosing interval. Plasma concentrations were drawn as follows: (1) for Cohorts 1-4 and 8 on Day 2 and Day 3 with Day 5 as optional; (2) for Cohorts 5-7 on Day 2 or Day 3.
Outcome Measure
PK Parameter: AUCtau of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State
Outcome Time Frame
Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hours
Secondary Ids
Secondary Id
2020-001803-17
Secondary Outcomes
Outcome Description
Clinical improvement was defined as ≥ 1-point and ≥ 2-point improvement from Baseline clinical status or recovery or discharged alive on 7-point ordinal scale. Recovery was defined as an improvement from a Baseline score of 2 - 5 to a score of 6 or 7 or an improvement from a Baseline score of 6 to 7 on the ordinal scale. The ordinal scale was used for the assessment of the clinical status at a given day using a 7-point ordinal scale with an increasing score indicating improvement. Scale: 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 RDV administration), 7=Not hospitalized. The 95% CI was based on the Clopper-Pearson method.
Outcome Time Frame
Day 10
Outcome Measure
Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score
Outcome Description
Time to discharge was the duration from the first dose date to getting discharged from the hospital.
Outcome Time Frame
From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Measure
Time (Days) to Discharge From Hospital
Outcome Description
Oxygen support status was derived from the 7-point ordinal scale score, 1 = death; 2 = invasive mechanical ventilation; 3 = high flow oxygen; 4 = low flow oxygen; 5 or 6 = room air; 7 = discharge. Change from Baseline for participants with oxygenation use status as '3=High Flow Oxygen', '4=Low Flow Oxygen' and '5=Room Air' at Baseline.
Outcome Time Frame
Day 10
Outcome Measure
Number of Participants With Change From Baseline in Oxygenation Use
Outcome Description
Mechanical ventilation status was derived from the 7-point ordinal scale score, 1 = death; 2 = invasive mechanical ventilation; 3 = high flow oxygen; 4 = low flow oxygen; 5 or 6 = room air; 7 = discharge.
Outcome Time Frame
Day 10
Outcome Measure
Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)
Outcome Description
Confirmed negative PCR is defined by as 2 consecutive negative PCR results or negative result at the last available sample for participants who completed or discontinued from the study. The assessment were done for the samples: nasal/oropharyngeal (OP), nasopharyngeal (NP)/oropharyngeal (OP), endotracheal (ET) aspirates, and rectal/fecal swabs.
Outcome Time Frame
From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Measure
Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result
Outcome Description
Change from baseline in SARS-CoV-2 viral load up to Day 10 or up to the first negative PCR result with confirmation (whichever comes first) were reported. The assessment were done for the samples: nasal/oropharyngeal (OP) samples, nasopharyngeal (NP)/OP samples, endotracheal (ET) aspirates, and rectal/fecal swabs.
Outcome Time Frame
Baseline, Day 10, and Day of Discharge (Day 10 or before)
Outcome Measure
Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load Up to Day 10 or Up to the First Confirmed Negative PCR Result
Outcome Time Frame
From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Measure
Bilirubin Concentrations in < 14-day-old Participants
Outcome Description
The PEWS was measured by 3 components, where 1= behavior, 2= perfusion assessed by capillary refill and heart rate, and 3= respiratory status assessed by respiratory rate, effort, and oxygen requirement. The score ranged between 0 to 9 point, with higher score representing the highest severity level. A negative change from baseline value indicated an improvement. Data are reported for participants with a PEWS behavior score ≥ 2 at baseline, and a ≥ 2-point improvement (indicated by a decrease) in PEWS behavior score by Day 10, participants with a PEWS behavior score ≥ 1 at baseline, with ≥ 1-point improvement in PEWS behavior score by Day 10 and participants who recovered in PEWS behavior, defined as a Baseline score of 1 through 3 improved to a score of 0.
Outcome Time Frame
Day 10
Outcome Measure
Percentage of Participants With Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale
Outcome Description
Plasma concentrations were drawn as follows: (1) for Cohorts 1-4 and 8 on Day 2 and Day 3, with Day 5 as optional; (2) for Cohorts 5-7 on Day 2 or Day 3.
Outcome Time Frame
Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hours
Outcome Measure
Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD)
Outcome Description
Participants who received at least one concomitant non-study COVID-19 medication from the first day of RDV treatment through the 30-day Follow-up visit or early withdrawal are reported.
Outcome Time Frame
first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Outcome Measure
Percentage of Participants With Concomitant Use of Medications Other Than RDV for Treatment of COVID-19
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
Maximum Age Number (converted to Years and rounded down)
18
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Goldman
Investigator Email
DAGOLDMA@montefiore.org
Investigator Phone
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