Evaluation of Safety, Pharmacokinetics, and Efficacy of GS-5245 in Pediatric Patients with COVID-19: A Phase 2/3 Single-Arm, Open-Label Study

Trial ID: 2023-503282-27-00
Protocol: GS-US-611-6464
Sponsor: Gilead Sciences Inc.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

COVID-19

Objectives

The primary objective of this study is to evaluate the **plasma pharmacokinetic** (PK) profile of Obeldesivir (ODV; GS-5245) in pediatric participants diagnosed with COVID-19. Additionally, the study aims to assess the safety and tolerability of ODV in this population. Understanding the pharmacokinetics and safety profile of ODV is crucial for determining appropriate dosing regimens and ensuring the safe administration of the drug in children and adolescents affected by COVID-19.

Secondary objectives include:

Assessing the impact of ODV on the time to sustained alleviation of targeted COVID-19 symptoms in pediatric participants.
Evaluating the antiviral activity of ODV on SARS-CoV-2 nasal swab viral load.
Assessing the impact of ODV on the requirement for supplemental oxygen.
Evaluating the palatability and acceptability of ODV.
Providing data on the use of medications other than remdesivir and ODV for COVID-19 treatment.
Assessing the impact of ODV on COVID-19-related hospitalizations or all-cause death.

Participants

The clinical trial involves a total of **30 participants** diagnosed with **COVID-19**. The study population includes both male and female pediatric subjects, ranging from **0 days to less than 18 years** of age. Participants were selected based on specific weight and gestational age criteria, with cohorts defined by age and weight categories. The trial population includes individuals with confirmed SARS-CoV-2 infection, verified by polymerase chain reaction (PCR) or an alternative molecular diagnostic assay within five days prior to screening. Participants exhibit initial COVID-19 symptoms such as fever, cough, or fatigue within five days before screening. The study also considers the presence of underlying medical conditions that may increase the risk of severe illness due to COVID-19, including obesity, diabetes, chronic lung disease, cardiac disease, immunosuppressive conditions, neurologic disorders, genetic conditions, and medical complexity. The trial includes a vulnerable population, ensuring comprehensive evaluation of the pharmacokinetics, safety, and tolerability of Obeldesivir (ODV; GS-5245) in this demographic.

Plans and Procedures

The clinical trial is designed to evaluate the **safety**, pharmacokinetics, and efficacy of Obeldesivir (ODV; GS-5245) in pediatric participants diagnosed with **COVID-19**. This study is a Phase 2/3, single-arm, open-label trial. The trial is expected to commence recruitment on January 1, 2024, and conclude by June 28, 2027. Participants will be administered GS-5245 in the form of film-coated tablets, with dosages of either 175 mg or 350 mg, taken orally. The maximum daily dose is 700 mg, with a total treatment period of up to 5 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and confirmed SARS-CoV-2 infection. The trial includes multiple cohorts based on age and weight, ranging from 0 days to less than 18 years. Follow-up visits will be conducted to monitor the pharmacokinetic parameters, safety, and any treatment-emergent adverse events (AEs) or laboratory abnormalities up to Day 35. The primary endpoints include the assessment of PK parameters such as AUC0-12, Cmax, and Ctrough for the ODV metabolite, GS-441524, and the incidence of treatment-emergent AEs. Secondary endpoints will evaluate the time to sustained alleviation of COVID-19 symptoms, changes in viral load, and the need for supplemental oxygen support.

The expected length of participant involvement is approximately 35 days, with conditions for early termination including the occurrence of severe adverse events or withdrawal of consent. Participants or their legal guardians must provide written informed consent, and assent will be obtained from participants where applicable. The trial aims to provide valuable data on the use of Obeldesivir in a pediatric population, contributing to the understanding of its role in treating COVID-19 in children and adolescents.

Treatment

The clinical trial involves the administration of **GS-5245**, a small molecule investigational drug, in the form of film-coated tablets. Two dosages are utilized: **GS-5245 tablets 175 mg** and **GS-5245 tablets 350 mg**. The active substance in both formulations is GS-5245, a chemical compound developed by Gilead Sciences Inc. The tablets are administered orally, with a maximum daily dose of 700 mg and a total maximum dose of 3500 mg over a treatment period of up to 5 days. The pharmaceutical form of the tablets is consistent across both dosages, ensuring uniformity in administration.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the safety, pharmacokinetics, and efficacy of GS-5245 in pediatric participants with COVID-19. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed as a single-arm, open-label study, allowing for direct observation of the drug's effects without the use of a control group.

Efficacy

The efficacy of the investigational product, **Obeldesivir** (ODV; GS-5245), in pediatric participants with COVID-19 will be assessed through a series of primary and secondary endpoints. Primary endpoints include the pharmacokinetic (PK) parameters of the ODV metabolite, GS-441524, specifically the area under the curve (AUC0-12), maximum concentration (Cmax), and trough concentration (Ctrough). Additionally, the incidence of treatment-emergent adverse events (AEs) and laboratory abnormalities will be monitored up to Day 35.

Secondary endpoints will evaluate the time to sustained alleviation of targeted COVID-19 symptoms by Day 35, changes from baseline in SARS-CoV-2 nasal swab viral load at Day 5, and the proportion of participants requiring supplemental oxygen support by Day 35. Other secondary measures include the assessment of palatability and acceptability scores of each formulation at Day 5, the proportion of participants using concomitant medications other than remdesivir and ODV for COVID-19 treatment by Day 35, and the proportion of participants experiencing COVID-19-related hospitalization or all-cause death by Day 35.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Participant or legal guardian willing and able to provide written informed consent prior to performing study procedures. Participants will provide assent, if possible, in accordance with local requirements and investigator’s discretion.
Aged < 18 years who meet one of the following weight criteria and gestational age (GA) criteria where applicable (where permitted according to local law and approved nationally and by relevant IRB or IEC): a) Cohort 1: ≥ 6 years to < 18 years and weight ≥ 40 kg b) Cohort 2: ≥ 6 years to < 18 years and weight ≥ 20 kg to < 40 kg c) Cohort 3: ≥ 2 years to < 18 years and weight ≥ 12 kg to < 20 kg d) Cohort 4: ≥ 28 days to < 18 years and weight ≥ 3 kg to < 12 kg e) Cohort 5: ≥ 14 days to < 28 days of age, GA ≥ 37 weeks and weight ≥ 2.5 kg f) Cohort 6: 0 days to < 14 days of age, GA ≥ 37 weeks and birth weight ≥ 2.5 kg g) Cohort 7: 0 days to < 56 days of age, GA < 37 weeks and birth weight ≥ 1.5 kg
SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) or an alternative molecular diagnostic assay ≤ 5 days before screening.
Initial onset of COVID-19 signs/symptoms ≤ 5 days before screening with ≥ 1 sign/symptom such as fever, cough, fatigue, shortness of breath, sore throat, headache, myalgia/arthralgia present at screening.
Presence of ≥ 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness due to COVID-19, including: a) obesity (body mass index > 95th percentile for age and sex) b) diabetes c) chronic lung disease (eg, asthma, interstitial lung disease) d) cardiac disease (eg, congenital heart disease) e) immunosuppressive disease or receipt of immunosuppressive therapies resulting in moderate or severe immunocompromise f) neurologic disorders (eg, epilepsy, convulsions, cerebral palsy) g) genetic conditions (eg, trisomy and other chromosomal abnormalities) h) medical complexity, including medical-related technological dependence that is not related to COVID-19 (eg, tracheostomy, positive pressure ventilation) i) other medical conditions that are deemed to be a risk factor by the investigator

cancel

Exclusion Criteria

Anticipated access to and use of authorized or approved COVID-19 therapies during the current COVID-19 illness < 5 days after screening (therapies including but not limited to nirmatrelvir/ritonavir, molnupiravir, intravenous RDV, monoclonal antibodies).
Vaccination for SARS-CoV-2 or self-reported history of SARS-CoV-2 infection < 4 months prior to screening.
Received any approved, authorized, or investigational direct acting antiviral drug against SARS-CoV-2 for the treatment of COVID-19 < 28 days or < 5 half-lives, whichever is longer, before enrollment.
Suspected or confirmed concurrent active systemic infection other than COVID-19 (including influenza) that may interfere with the evaluation of response to the study intervention.
Any of the following abnormal laboratory results at screening: a. ALT ≥ 5 × ULN b. eGFR < 60 mL/min/1.73 m2 for ≥ 1 year of age c. Serum creatinine: > 2.0 mg/dL for < 48 hours of life; > 2 × ULN for age for ≥ 48 hours of life to 1 year of age (refer to table on page 35 of protocol)
Any major congenital renal anomaly for participants < 28 days of age.
Apgar score < 5 for participants < 24 hours of age.
Known hypersensitivity to the study drug, the metabolites, or formulation excipient.
Positive pregnancy test prior to enrollment for female participants of childbearing potential
Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.3.1. of the protocol

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	01 Jan 2024	6
Hungary	Not Recruiting	01 Jan 2024	3
Italy	Not Recruiting	01 Jan 2024	3
Poland	Not Recruiting	01 Jan 2024	4
Spain	Not Recruiting	01 Jan 2024	6