Clinical trial NCT04431453: Study of Remdesivir in Participants Below 18 Years Old With COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-06-16
Enrollment: 59
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

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

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
measure: Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities
timeFrame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
measure: Pharmacokinetic (PK) Parameter: Cmax of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State
timeFrame: 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
measure: PK Parameter: AUCtau of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State
timeFrame: 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 outcomes:
measure: Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score
timeFrame: Day 10
measure: Time (Days) to Discharge From Hospital
timeFrame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
measure: Number of Participants With Change From Baseline in Oxygenation Use
timeFrame: Day 10
measure: Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: Day 10
measure: Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result
timeFrame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
measure: 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
timeFrame: Baseline, Day 10, and Day of Discharge (Day 10 or before)
measure: Bilirubin Concentrations in < 14-day-old Participants
timeFrame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
measure: Percentage of Participants With Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale
timeFrame: Day 10
measure: Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD)
timeFrame: 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
measure: Percentage of Participants With Concomitant Use of Medications Other Than RDV for Treatment of COVID-19
timeFrame: first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan University of California, Los Angeles Medical Center
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Sacramento
country: United States
facility: UC Davis Medical center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Tampa
country: United States
facility: Tampa General Hospital (Inpatient Visits)
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital
state: Illinois
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health/Helen De Vos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Minnesota
state: Minnesota
city: Bronx
country: United States
facility: NYC Health + Hospitals/Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health-Cohen Children's Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center-Levine Children's Hospital
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Meyer
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino
city: Parma
country: Italy
facility: UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Esplugues de llobregat
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.