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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 32
- 主要终点
- Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities
研究概览
简要总结
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).
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg
Participants will receive RDV 200 mg, intravenous (IV) infusion on Day 1 followed by RDV 100 mg, IV infusion, daily, up to 10 days.
干预措施: Remdesivir (Drug)
RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg
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.
干预措施: Remdesivir (Drug)
RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg
Participants will receive RDV 200 mg, IV infusion on Day 1 followed by RDV 100 mg, IV infusion daily up to 10 days.
干预措施: Remdesivir (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Number of Participants With Change From Baseline in Oxygenation Use(Day 10)
- Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)(Day 10)
- Percentage of Participants With Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale(Day 10)
- 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)
- Time (Days) to Discharge From Hospital(From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days))
- 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))
- 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))
- Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score(Day 10)
- 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))