Study of Remdesivir in Participants Below 18 Years Old With COVID-19 (CARAVAN)

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

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).

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Remdesivir

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: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Italy
  • Florence, Italy, 50139
    • Azienda Ospedaliero Universitaria Meyer
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino
  • Parma, Italy, 43126
    • UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Esplugues de llobregat, Spain, 8950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28041
    • Hospital Universitario La Paz
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario de Santiago
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095
      • Ronald Reagan University of California, Los Angeles Medical Center
    • Madera, California, United States, 93636
      • Valley Children's Hospital
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital (Inpatient Visits)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Children's Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health/Helen De Vos Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Minnesota
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Bronx, New York, United States, 10461
      • NYC Health + Hospitals/Jacobi Medical Center
    • New Hyde Park, New York, United States, 11040
      • Northwell Health-Cohen Children's Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center-Levine Children's Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hospital for Children
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Experimental: 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.	Drug: Remdesivir; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities	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.	From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Pharmacokinetic (PK) Parameter: Cmax of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State	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.	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
PK Parameter: AUCtau of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score	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.	Day 10
Time (Days) to Discharge From Hospital	Time to discharge was the duration from the first dose date to getting discharged from the hospital.	From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Number of Participants With Change From Baseline in Oxygenation Use	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.	Day 10
Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)	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.	Day 10
Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result	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.	From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
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	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.	Baseline, Day 10, and Day of Discharge (Day 10 or before)
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 Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale	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.	Day 10
Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD)	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.	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
Percentage of Participants With Concomitant Use of Medications Other Than RDV for Treatment of COVID-19	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.	first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Ahmed A, Rojo P, Agwu A, Kimberlin D, Deville J, Mendez-Echevarria A, et al. Remdesivir Treatment for COVID-19 in Hospitalized Children: CARAVAN Interim Results [Presentation]. European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022; 2022 23-26 April; Lisbon, Portugal and Online.
• Ahmed A, Rojo P, Agwu A, Kimberlin D, Deville J, Mendez-Echevarria A, et al. Remdesivir Treatment for COVID-19 in Hospitalized Children: CARAVAN Interim Results [Presentation]. Virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2022; 2022c 12-16 February.
• Munoz F, Muller W, Ahmed A, Kimberlin D, Mendez-Echevarria A, Chen JS, et al. Safety and efficacy of Remdesivir in a pediatric COVID-19 population (CROI) [Abstract 617]. Topics in antiviral medicine 2021;29 (1):237.
• Pikora C, Bamford A, Luzuriaga K, Wiznia A, Rojo Conejo P, Muller B, et al. Challenges of remdesivir pediatric development for SARS-CoV-2 infection in a pandemic. 12th International Workshop on HIV Pediatrics; 2020 November 16-17; Virtual Event.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): February 10, 2023
• Study Completion (Actual): February 10, 2023

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 6, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: GS-US-540-5823; 2020-001803-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No