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Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Remdesivir (GS-5734™) in Participants From Birth to < 18 Years of Age With Coronavirus Disease 2019 (COVID-19) (CARAVAN)

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ClinicalTrials.gov Identifier: NCT04431453
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : July 23, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE June 8, 2020
First Posted Date  ICMJE June 16, 2020
Last Update Posted Date July 23, 2021
Actual Study Start Date  ICMJE July 21, 2020
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
  • Proportion of Participants Experiencing any Treatment-Emergent Adverse Events [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Plasma Concentrations of Remdesivir (RDV) and Metabolites [ 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 ]
    Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 and cohort 8 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Original Primary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
  • Proportion of Participants Experiencing any Treatment-Emergent Adverse Events [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Plasma Concentrations of Remdesivir (RDV) and Metabolites [ 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 ]
    Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
  • Change From Baseline in Oxygenation Use [ Time Frame: Baseline, up to Day 30 Follow-up Assessment ]
  • Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: Baseline, up to Day 30 Follow-up Assessment ]
  • Clinical Improvement on a 7-point Ordinal Scale [ Time Frame: First dose date up to 10 days ]
    The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1.) Death 2.) Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (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 (coronavirus (COVID-19) related or otherwise) 6.) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration) 7.) Not hospitalized.
  • Time (days) to Discharge From Hospital [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result [ Time Frame: First dose date up to 10 days ]
    Confirmed negative PCR is defined by 2 consecutive negative PCR results.
  • Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load [ Time Frame: Baseline, up to 10 days or up to the first confirmed negative PCR results (whichever comes first) ]
  • Bilirubin Concentrations in < 14-day-old Participants [ Time Frame: First dose date up to 10 days ]
  • Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale [ Time Frame: First dose date up to 10 days ]
    The PEWS is measured by 3 components, including 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 ranges between zero to 9 point, with 9 point representing the highest severity level.
  • Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD) [ 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 ]
    Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 and cohort 8 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
  • Proportion of Participants With Concomitant Use of Medications other than RDV for Treatment of Coronavirus Disease 2019 (COVID-19) [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
  • Change From Baseline in Oxygenation Use [ Time Frame: Baseline, up to Day 30 Follow-up Assessment ]
  • Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: Baseline, up to Day 30 Follow-up Assessment ]
  • Clinical Improvement on a 7-point Ordinal Scale [ Time Frame: First dose date up to 10 days ]
    The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1.) Death 2.) Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (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 (coronavirus (COVID-19) related or otherwise) 6.) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration) 7.) Not hospitalized.
  • Time (days) to Discharge From Hospital [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
  • Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result [ Time Frame: First dose date up to 10 days ]
    Confirmed negative PCR is defined by 2 consecutive negative PCR results.
  • Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load [ Time Frame: Baseline, up to 10 days or up to the first confirmed negative PCR results (whichever comes first) ]
  • Bilirubin Concentrations in < 14-day-old Participants [ Time Frame: First dose date up to 10 days ]
  • Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale [ Time Frame: First dose date up to 10 days ]
    The PEWS is measured by 3 components, including 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 ranges between zero to 9 point, with 9 point representing the highest severity level.
  • Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD) [ 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 ]
    Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
  • Proportion of Participants With Concomitant Use of Medications other than RDV for Treatment of Coronavirus Disease 2019 (COVID-19) [ Time Frame: First dose date up to Day 30 Follow-up Assessment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Remdesivir (GS-5734™) in Participants From Birth to < 18 Years of Age With Coronavirus Disease 2019 (COVID-19)
Official Title  ICMJE 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
Brief Summary The primary objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of remdesivir (RDV) in participants with laboratory-confirmed coronavirus disease 2019 (COVID-19) aged 0 days to < 18 years.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Drug: Remdesivir
Administered as an intravenous infusion
Other Names:
  • GS-5734™
  • Veklury®
Study Arms  ICMJE Experimental: Remdesivir (RDV)

Participants will receive RDV up to 10 days. The RDV dose administered in each cohort is as follows:

  • Cohort 1: intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg daily
  • Cohorts 2-5: IV RDV 5 mg/kg on Day 1 followed by IV RDV 2.5 mg/kg daily
  • Cohort 6-7: IV RDV at a dose to be determined based on RDV exposure data from Cohort 5
  • Cohort 8: IV RDV 200 mg on Day 1 followed by IV RDV 100 mg daily
Intervention: Drug: Remdesivir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2020)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04431453
Other Study ID Numbers  ICMJE GS-US-540-5823
2020-001803-17 ( EudraCT Number )
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  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP