COVID-19Phase 2/3CARAVANNCT04431453

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

A Phase 2/3 study testing Remdesivir in people with COVID-19, run by Gilead Sciences at 32 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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). Read more about this study

Who is it for?: Ages Up to 18 years
Conditions the study is for: COVID-19
What is being tested?: Remdesivir
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 59 participants
Where: 32 sitesin 4 countries
Study dates: 21 Jul 2020to 10 Feb 2023
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Show all 9Show fewer

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).

Who cannot join

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

Trial locations and contacts

32 sites in 4 countries.

Country

City, postcode or hospital

32 sites in 4 countries

United States22 sites

Lehigh Valley Hospital/Lehigh Valley Health Network (LVH/LVHN)
Allentown, Pennsylvania, 18103
Johns Hopkins Children's Center
Baltimore, Maryland, 21287
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
Carolinas Medical Center-Levine Children's Hospital
Charlotte, North Carolina, 28203
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Children's Medical Center
Dallas, Texas, 75235
Spectrum Health/Helen De Vos Children's Hospital
Grand Rapids, Michigan, 49503
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Ronald Reagan University of California, Los Angeles Medical Center
Los Angeles, California, 90095
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
Children's Minnesota
Minneapolis, Minnesota, 55404
Northwell Health-Cohen Children's Medical Center
New Hyde Park, New York, 11040
Tulane University School of Medicine
New Orleans, Louisiana, 70112
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
UC Davis Medical center
Sacramento, California, 95817
Rady Children's Hospital San Diego
San Diego, California, 92123
Tampa General Hospital (Inpatient Visits)
Tampa, Florida, 33606
NYC Health + Hospitals/Jacobi Medical Center
The Bronx, New York, 10461
Montefiore Medical Center
The Bronx, New York, 10467

Other trials in United States

Spain6 sites

Hospital Universitari Vall D'Hebron
Barcelona, 8035
Hospital Sant Joan de Déu
Esplugues de Llobregat, 8950
Hospital General Universitario Gregorio Maranon
Madrid, 28009
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28041
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15706

Other trials in Spain

Italy3 sites

Azienda Ospedaliero Universitaria Meyer
Florence, 50139
Azienda Ospedaliera di Padova - Dipartimento Salute della Donna e del Bambino
Padova, 35128
UO Clinica Pediatrica, Ospedale Pietro Barilla - AOU di Parma
Parma, 43126

Other trials in Italy

United Kingdom1 site

Alder Hey Children's NHS Foundation Trust
Liverpool, L12 2AP

Other trials in United Kingdom

About this study

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

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).

Read the 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

Conditions: COVID-19
Being tested: Remdesivir
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RemdesivirDrug
Also called GS-5734™, Veklury®
Administered as an intravenous infusion

Study groups in NCT04431453
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Remdesivir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Day 10, and Day of Discharge (Day 10 or before)
Bilirubin Concentrations in < 14-day-old Participants
Measured: 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.
Measured: 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.
Measured: 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.
Measured: first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Jul 202010 Feb 2023

First posted16 Jun 2020
Study start21 Jul 2020
Primary completion10 Feb 2023
Study completion10 Feb 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for COVID-19Studies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 59 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04431453
Sponsor's protocol ID: GS-US-540-5823
Other IDs: 2020-001803-17
Acronym: CARAVAN
Status last verified: Jan 2024
First submitted: 8 Jun 2020
Last updated: 6 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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
Expanded access: Available

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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04431453
Acronym / sponsor ID: CARAVAN / GS-US-540-5823
Conditions: COVID-19
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 59 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 21 Jul 2020 (actual)
Primary completion: 10 Feb 2023 (actual)
Study completion: 10 Feb 2023 (actual)
First posted: 16 Jun 2020 (actual)
Results: Posted 22 Dec 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg	Experimental	Drug: RemdesivirParticipants will receive RDV 200 mg, intravenous (IV) infusion on Day 1 followed by RDV 100 mg, IV infusion, daily, up to 10 days.
RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg	Experimental	Drug: RemdesivirParticipants 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.
RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg	Experimental	Drug: RemdesivirParticipants will receive RDV 200 mg, IV infusion on Day 1 followed by RDV 100 mg, IV infusion daily up to 10 days.

Who may qualify

Ages: Up to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (9 listed)

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)).
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 (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RemdesivirAlso: GS-5734™, Veklury®Administered as an intravenous infusion	Drug	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

Primary outcome

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

10 secondary outcomes

Percentage of Participants With Clinical Improvement on a 7-point Ordinal Scale Score
Time frame: Day 10
Time (Days) to Discharge From Hospital
Time frame: 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
Time frame: Day 10
Number of Participants With Change From Baseline in the Use of Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)
Time frame: Day 10
Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result
Time frame: 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
Time frame: Baseline, Day 10, and Day of Discharge (Day 10 or before)
Bilirubin Concentrations in < 14-day-old Participants
Time frame: 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
Time frame: Day 10
Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD)
Time frame: 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
Time frame: first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)

Results and safety

Results posted to the registry on 22 Dec 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg	12	11
RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg	12	11
RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg	12	11
RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg	12	9
RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg	4	3
RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg	1	1
RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg	1	1
RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg	5	4

Primary outcome: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

Time frame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days). Number. Unit: percentage of participants

Measure	Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg n = 12	RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg n = 12	RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg n = 12	RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg n = 12	RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg n = 3	RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg n = 0	RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg n = 0	RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg n = 5
Value	91.7	58.3	75.0	58.3	66.7	–	–	80.0

Population analysed: Safety Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug. Data for Cohorts 6 and 7 were not reported due to participants' confidentiality reasons as there was only 1 participant in each of these groups.

Primary outcome: Percentage of Participants With Treatment-Emergent Graded Laboratory Abnormalities

Time frame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days). Number. Unit: percentage of participants

Measure	Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg n = 12	RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg n = 12	RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg n = 12	RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg n = 11	RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg n = 3	RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg n = 0	RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg n = 0	RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg n = 5
Any grade	100	83.3	91.7	90.9	100	–	–	80
Grade 3 or 4	75	16.7	41.7	36.4	100	–	–	60

Population analysed: Participants in the Safety Analysis Set with at least 1 postbaseline value for the test under evaluation were analyzed. Data for Cohorts 6 and 7 were not reported due to participants' confidentiality reasons as there was only 1 participant in each of these groups.

Primary outcome: Pharmacokinetic (PK) Parameter: Cmax of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State

Time frame: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg n = 12	RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg n = 12	RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg n = 11	RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg n = 10	RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg n = 3	RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg n = 0	RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg n = 0	RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg n = 5
Remdesivir	4108.7 (1365.15)	6003.5 (1879.86)	5980.1 (2284.08)	5192.9 (2066.65)	4829.0 (956.16)	–	–	4235.7 (1790.53)
GS-704277	360.6 (208.11)	469.0 (239.72)	484.8 (244.07)	407.8 (132.45)	466.0 (110.87)	–	–	297.9 (160.18)
GS-441524	276.4 (327.14)	210.5 (121.02)	186.5 (103.09)	209.8 (49.73)	371.8 (151.10)	–	–	230.4 (255.03)

Population analysed: The RDV and Metabolites PK Analysis Set included all enrolled participants who received at least 1 dose of RDV and for whom PK concentrations of RDV and metabolites were available. Data for Cohorts 6 and 7 were not reported due to participants' confidentiality reasons as there was only 1 participant in each of these groups.

Primary outcome: PK Parameter: AUCtau of Remdesivir and Its Metabolites GS-704277 and GS-441524 at Steady State

Measure	Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg n = 12	RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg n = 12	RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg n = 11	RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg n = 10	RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg n = 3	RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg n = 0	RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg n = 0	RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg n = 5
Remdesivir	2630.1 (923.85)	3937.9 (1981.40)	6752.1 (10911.98)	3625.7 (3361.19)	2650.3 (587.77)	–	–	2519.6 (1235.49)
GS-704277	1222.9 (1348.12)	860.3 (512.58)	876.0 (720.39)	776.0 (485.18)	1049.0 (253.73)	–	–	671.4 (553.30)
GS-441524	5486.2 (7599.27)	3016.1 (2425.78)	2751.8 (1868.93)	2969.1 (940.73)	6899.3 (3910.28)	–	–	4336.8 (5692.30)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality: First dose date up to approximately 8 weeks Adverse events: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Remdesivir (RDV), Cohort 1: Age 12 to <18 Years and Weight ≥40 kg	5 of 12 (41.7%)	11 of 12 (91.7%)	2 of 12
RDV, Cohort 2: Age ≥ 28 Days to < 18 Years and Weight ≥ 20 kg to < 40 kg	2 of 12 (16.7%)	7 of 12 (58.3%)	1 of 12
RDV, Cohort 3: Age ≥ 28 Days to < 18 Years and Weight ≥ 12 kg to < 20 kg	0 of 12 (0%)	9 of 12 (75%)	0 of 12
RDV, Cohort 4: Age ≥ 28 Days to < 18 Years and Weight ≥ 3 kg to < 12 kg.	3 of 12 (25%)	7 of 12 (58.3%)	0 of 12
RDV,Cohort 5: Age ≥14 - <28 Days of Age, Gestational Age >37 Weeks, and Weight at Baseline ≥2.5 kg	1 of 3 (33.3%)	2 of 3 (66.7%)	0 of 4
RDV, Cohort 6: Age 0 to < 14 Days of Age, Gestational Age > 37 Weeks, and Birth Weight ≥ 2.5 kg	0 of 0	0 of 0	0
RDV, Cohort 7: Age 0 to < 56 Days of Age, Gestational Age ≤ 37 Weeks, and Birth Weight ≥ 1.5 kg	0 of 0	0 of 0	0
RDV, Cohort 8: < 12 Years and Weight ≥ 40 kg	1 of 5 (20%)	4 of 5 (80%)	1 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundAhmed 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.
BackgroundAhmed 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.
BackgroundMunoz 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.
BackgroundPikora 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.
Gilead Clinical Trials WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

32 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Remdesivir in people with COVID-19, run by Gilead Sciences at 32 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Spain, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From first dose date (Day 1) up to follow-up assessment (maximum duration: 30 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04431453, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.