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

NCT04431453 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-540-58232020-001803-17
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 32

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).

Conditions

COVID-19

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (10)

• Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score

  Day 10

• Time (Days) to Discharge From 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

  Day 10

• Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)

  Day 10

• Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result

  From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)

Study Arms (8)

Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg

EXPERIMENTAL

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

RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg

EXPERIMENTAL

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

RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg

EXPERIMENTAL

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

RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg

EXPERIMENTAL

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

RDV, Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg

EXPERIMENTAL

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

RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg

EXPERIMENTAL

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

RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg

EXPERIMENTAL

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

RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg

EXPERIMENTAL

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

Interventions

Remdesivir DRUG

Administered as an intravenous infusion

Also known as: GS-5734™, Veklury®

RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg; RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg; RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg; RDV, Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg; RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg; RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg; RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg; Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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)).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (32)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Ronald Reagan University of California, Los Angeles Medical Center

Los Angeles, California, 90095, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

UC Davis Medical center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Tampa General Hospital (Inpatient Visits)

Tampa, Florida, 33606, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Children's Center

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Spectrum Health/Helen De Vos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Northwell Health-Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

NYC Health + Hospitals/Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolinas Medical Center-Levine Children's Hospital

Charlotte, North Carolina, 28203, United States

Location

Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)

Allentown, Pennsylvania, 18103, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Azienda Ospedaliero Universitaria Meyer

Florence, 50139, Italy

Location

Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino

Padua, 35128, Italy

Location

UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma

Parma, 43126, Italy

Location

Hospital Universitari Vall D'Hebron

Barcelona, 8035, Spain

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, 8950, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28041, Spain

Location

Hospital Clínico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Related 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

COVID-19

Interventions

remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 16, 2020
• Study Start: July 21, 2020
• Primary Completion: February 10, 2023
• Study Completion: February 10, 2023
• Last Updated: February 6, 2024
• Results First Posted: December 22, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

GB (1); ES (6); US (22); IT (3)