Study of Remdesivir in Participants Below 18 Years Old With COVID-19
- Registration Number
- NCT04431453
- Lead Sponsor
- Gilead Sciences
- 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).
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
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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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg Remdesivir Participants will receive RDV 5 mg/kg, IV infusion on Day 1 followed by RDV 2.5 mg/kg mg, IV infusion, daily, up to 10 days. Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg Remdesivir Participants will receive RDV 200 mg, intravenous (IV) infusion on Day 1 followed by RDV 100 mg, IV infusion, daily, up to 10 days. RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg Remdesivir Participants will receive RDV 5 mg/kg, IV infusion on Day 1 followed by RDV 2.5 mg/kg mg, IV infusion, daily, up to 10 days. RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg Remdesivir Participants will receive RDV 5 mg/kg, IV infusion on Day 1 followed by RDV 2.5 mg/kg mg, IV infusion, daily, up to 10 days. RDV, Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg Remdesivir Participants will receive RDV 5 mg/kg, IV infusion on Day 1 followed by RDV 2.5 mg/kg mg, IV infusion, daily, up to 10 days. RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg Remdesivir Participants will receive RDV 2.5 mg/kg, IV infusion on Day 1 followed by RDV 1.25 mg/kg mg, IV, daily, up to 10 days. RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg Remdesivir Participants will receive RDV 2.5 mg/kg, IV infusion on Day 1 followed by RDV 1.25 mg/kg mg, IV, daily, up to 10 days. RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg Remdesivir Participants will receive RDV 200 mg, IV infusion on Day 1 followed by RDV 100 mg, IV infusion daily up to 10 days.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) 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.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) 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.
PK Parameter: AUCtau of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State 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 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.
Pharmacokinetic (PK) Parameter: Cmax of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State 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 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Change From Baseline in Oxygenation Use Day 10 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.
Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Day 10 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.
Percentage of Participants With Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale Day 10 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.
Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD) 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 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.
Time (Days) to Discharge From Hospital From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) Time to discharge was the duration from the first dose date to getting discharged from the hospital.
Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) 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.
Bilirubin Concentrations in < 14-day-old Participants From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) Percentage of Participants With Concomitant Use of Medications Other Than RDV for Treatment of COVID-19 first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days) 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.
Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score Day 10 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.
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 Baseline, Day 10, and Day of Discharge (Day 10 or before) 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.
Trial Locations
- Locations (32)
Johns Hopkins Children's Center
🇺🇸Baltimore, Maryland, United States
Rady Children's Hospital San Diego
🇺🇸San Diego, California, United States
Ann & Robert H. Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Carolinas Medical Center-Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Ronald Reagan University of California, Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino
🇮🇹Padova, Italy
Children's Minnesota
🇺🇸Minneapolis, Minnesota, United States
UC Davis Medical center
🇺🇸Sacramento, California, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Tampa General Hospital (Inpatient Visits)
🇺🇸Tampa, Florida, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Spectrum Health/Helen De Vos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Northwell Health-Cohen Children's Medical Center
🇺🇸New Hyde Park, New York, United States
Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)
🇺🇸Allentown, Pennsylvania, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Azienda Ospedaliero Universitaria Meyer
🇮🇹Florence, Italy
UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma
🇮🇹Parma, Italy
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Sant Joan de Déu
🇪🇸Esplugues de llobregat, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Alder Hey Children's NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Children's Medical Center
🇺🇸Dallas, Texas, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
NYC Health + Hospitals/Jacobi Medical Center
🇺🇸Bronx, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States