CARAVAN: 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)

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04431453
• Collaborator: (none)
• Enrollment: 62
• Locations: 37
• Arm: 1
• Anticipated Duration (Months): 30.4
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Remdesivir	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 21, 2020
• Anticipated Primary Completion Date: Feb 1, 2023
• Anticipated Study Completion Date: Feb 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

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 2.5 mg/kg on Day 1 followed by IV RDV 1.25 mg/kg daily for up to 10 days Cohort 8: IV RDV 200 mg on Day 1 followed by IV RDV 100 mg daily

Drug: Remdesivir; Administered as an intravenous infusion; Other Names: GS-5734™ Veklury®

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants Experiencing any Treatment-Emergent Adverse Events [First dose date up to Day 30 Follow-up Assessment]

2. Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities [First dose date up to Day 30 Follow-up Assessment]

3. Plasma Concentrations of Remdesivir (RDV) and Metabolites [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.

Secondary Outcome Measures

1. Change From Baseline in Oxygenation Use [Baseline, up to Day 30 Follow-up Assessment]

2. Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) [Baseline, up to Day 30 Follow-up Assessment]

3. Clinical Improvement on a 7-point Ordinal Scale [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.

4. Time (days) to Discharge From Hospital [First dose date up to Day 30 Follow-up Assessment]

5. Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result [First dose date up to 10 days]

   Confirmed negative PCR is defined by 2 consecutive negative PCR results.

6. Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load [Baseline, up to 10 days or up to the first confirmed negative PCR results (whichever comes first)]

7. Bilirubin Concentrations in < 14-day-old Participants [First dose date up to 10 days]

8. Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale [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.

9. 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 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.

10. Proportion of Participants With Concomitant Use of Medications other than RDV for Treatment of Coronavirus Disease 2019 (COVID-19) [First dose date up to Day 30 Follow-up Assessment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)).

• 1. Cohort 1: ≥ 12 years to < 18 years of age and weight at screening ≥ 40 kg
• 1. Cohorts 2-4: ≥ 28 days to < 18 years of age and weight at screening ≥ 3 kg and < 40 kg
• 1. Cohort 5: ≥ 14 days to < 28 days of age, gestational age > 37 weeks and weight at screening ≥ 2.5 kg
• 1. Cohort 6: 0 days to < 14 days of age, gestational age > 37 weeks and birth weight of ≥ 2.5 kg
• 1. Cohort 7: 0 days to < 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
• 1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	Ronald Reagan University of California, Los Angeles Medical Center	Los Angeles	California	United States	90095
4	Valley Children's Hospital	Madera	California	United States	93636
5	Rady Children's Hospital San Diego	San Diego	California	United States	92123
6	Tampa General Hospital (Inpatient Visits)	Tampa	Florida	United States	33606
7	Ann & Robert H. Lurie Children's Hospital	Chicago	Illinois	United States	60611
8	Norton Children's Hospital	Louisville	Kentucky	United States	40202
9	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
10	Johns Hopkins Children's Center	Baltimore	Maryland	United States	21287
11	Boston Children's Hospital	Boston	Massachusetts	United States	02115
12	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01605
13	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
14	Spectrum Health/Helen De Vos Children's Hospital	Grand Rapids	Michigan	United States	49503
15	Children's Minnesota	Minneapolis	Minnesota	United States	55404
16	Children's Hospital & Medical Center	Omaha	Nebraska	United States	68114
17	NYC Health + Hospitals/Jacobi Medical Center	Bronx	New York	United States	10461
18	Montefiore Medical Center	Bronx	New York	United States	10467
19	Northwell Health-Cohen Children's Medical Center	New Hyde Park	New York	United States	11040
20	Carolinas Medical Center-Levine Children's Hospital	Charlotte	North Carolina	United States	28203
21	Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)	Allentown	Pennsylvania	United States	18103
22	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
23	Children's Medical Center	Dallas	Texas	United States	75235
24	Texas Children's Hospital	Houston	Texas	United States	77030
25	Azienda Ospedaliero Universitaria Meyer	Florence		Italy	50139
26	University Hospital of Padova, Clinic of Pediatric Hematology-Oncology	Padova		Italy	35128
27	University Hospital of Parma	Parma		Italy	43126
28	Hospital Universitari Vall D'Hebron	Barcelona		Spain	8035
29	Hospital Sant Joan de Déu	Esplugues de llobregat		Spain	8950
30	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28009
31	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
32	Hospital Universitario La Paz	Madrid		Spain	28041
33	Hospital Clínico Universitario de Santiago	Santiago de Compostela		Spain	15706
34	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B95SS
35	Alder Hey Children's NHS Foundation Trust	Liverpool		United Kingdom	L12 2AP
36	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 7EU
37	King's College NHS Foundation Trust	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Gilead Clinical Trials Website

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT04431453
• Other Study ID Numbers: GS-US-540-5823; 2020-001803-17
• First Posted: Jun 16, 2020
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Remdesivir

Study Results

No Results Posted as of Aug 19, 2022