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

COVID-19 Clinical Trial

— CARAVAN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04431453
• Other study ID #: GS-US-540-5823
• Secondary ID: 2020-001803-17
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 21, 2020
• Est. completion date: February 10, 2023

Study information

• Verified date: January 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 10, 2023
• Est. primary completion date: February 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Remdesivir
Administered as an intravenous infusion

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero Universitaria Meyer	Florence
Italy	Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino	Padova
Italy	UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma	Parma
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Sant Joan de Déu	Esplugues de llobregat
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
United States	Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)	Allentown	Pennsylvania
United States	Johns Hopkins Children's Center	Baltimore	Maryland
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	NYC Health + Hospitals/Jacobi Medical Center	Bronx	New York
United States	Carolinas Medical Center-Levine Children's Hospital	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital	Chicago	Illinois
United States	Children's Medical Center	Dallas	Texas
United States	Spectrum Health/Helen De Vos Children's Hospital	Grand Rapids	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Ronald Reagan University of California, Los Angeles Medical Center	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Valley Children's Hospital	Madera	California
United States	Children's Minnesota	Minneapolis	Minnesota
United States	Northwell Health-Cohen Children's Medical Center	New Hyde Park	New York
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	UC Davis Medical center	Sacramento	California
United States	Rady Children's Hospital San Diego	San Diego	California
United States	Tampa General Hospital (Inpatient Visits)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Italy,  Spain,  United Kingdom, 

References & Publications (4)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Bilirubin Concentrations in < 14-day-old Participants		From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Secondary	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
Secondary	Plasma Concentrations of Sulfobutylether ß-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
Secondary	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)

External Links

•   Gilead Clinical Trials Website