RSV Infection
Conditions
Brief summary
The goal of this clinical study is to check if obeldesivir (ODV; GS-5245) is safe and well-tolerated by children with respiratory syncytial virus (RSV) infection. It will also look at how well ODV helps reduce the time it takes for children to feel better and for their RSV symptoms to improve. The primary objectives of this study are: a) to evaluate the safety and tolerability of ODV in pediatric participants with RSV infection; b) To evaluate the efficacy of ODV on time to alleviation of targeted RSV symptoms in pediatric participants with RSV infection.
Detailed description
Pediatric participants will be enrolled as follows: * Cohort 1: Infants and children from 4 weeks postnatal age, weighing ≥ 1.5 kg to \< 40 kg * Cohort 2: Neonates, either born at term or preterm, weighing ≥ 1.5 kg to \< 6 kg
Interventions
DRUGObeldesivir
Administered orally
Administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants assigned male or female at birth, from birth to \< 5 years of age who meet one of the following criteria, where permitted according to local law and approved nationally and by relevant institutional review board or independent ethics committee: * Cohort 1: Infants and children from 4 weeks postnatal age, weighing ≥ 3 kg to \< 40 kg (Part A) and ≥ 1.5 kg to \< 3 kg (Part B) * Cohort 2: Neonates, either born at term or preterm, weighing ≥ 1.5 kg to \< 6 kg * RSV infection diagnosis ≤ 3 days prior to randomization. * Negative test for influenza A/B, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection) ≤ 7 days prior to randomization. * Onset of RSV signs or symptoms ≤ 3 days prior to randomization. * Presence of at least 1 sign or symptom of RSV infection at screening and at randomization. Key
Exclusion criteria
* Currently requiring or expected to require hospitalization for RSV infection within 48 hours after randomization. * Not expected to survive the current RSV-related illness. * Documented previous infection and/or hospitalization for RSV during the current respiratory virus season. * Diagnosed with acute concurrent active systemic infections requiring treatment with systemic antiviral, antibacterial, antifungal, or antimycobacterial therapy, or with any documented respiratory viral infection (other than RSV), ≤ 7 days prior to randomization. * History of asthma or recurrent wheezing. * Neuromuscular disease that affects swallowing. * Cystic fibrosis. * Participants who are immunocompromised. * Alanine aminotransferase ≥ 5 × upper limit of normal (ULN). * Abnormal renal function. * Concurrent or previous treatment with other agents with actual or possible direct antiviral activity against RSV, received within 28 days or within 5 half-lives, whichever is longer, prior to randomization. * Received palivizumab within 100 days, or nirsevimab within 1 year, or other RSV specific monoclonal antibody within 5 half-lives of the antibody, prior to randomization. * Participant whose mother received RSV vaccination during pregnancy and who is \< 1 year old prior to randomization. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) by Day 28 | Up to Day 28 | TEAEs were defined as any adverse events that began on or after the date of first dose of study drug up to the date of last dose of study drug up to Day 28. The percentage of participants who experienced at least one TEAE was assessed from Day 1 through Day 28. |
| Percentage of Participants Who Experienced Grade 3 or 4 Treatment-Emergent Laboratory Abnormalities by Day 28 | Up to Day 28 | A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose up to Day 28. A treatment-emergent laboratory abnormality severity was graded according to the Division of AIDS (DAIDS) Version 2.1. Grade 0: Values that do not meet the criteria for an abnormality of at least Grade 1;Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially life-threatening. The percentage of participants who experienced Grade 3 or 4 laboratory abnormalities was assessed from Day 1 through Day 28. |
| Time to Alleviation of Targeted Respiratory Syncytial Virus (RSV) Symptoms by Day 28 | Up to Day 28 | Alleviation of targeted RSV symptoms was defined as achievement of 2 consecutive daily assessments with improvement in score by at least 1 point for any targeted RSV symptom with baseline score is \> 1, or no increase in score for any targeted RSV symptom with baseline score of 1, assessed from Day 1 to Day 28. The time to alleviation of targeted RSV symptoms by Day 28 was calculated as the symptom alleviation date minus the first dose date. Targeted RSV symptoms referred to the RSV symptoms (cough, respiratory signs, RSV signs, behavior impact). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: AUCtau of GS-441524, Metabolite of Obeldesivir | Day 5 (predose, 2.5, and 3.5 hours post-dose) | AUCtau is defined as area under the plasma concentration-time curve during a dosing interval (AUCtau) of GS-441524, the active metabolite of obeldesivir. |
| PK Parameter: Cmax of GS-441524, Metabolite of Obeldesivir | Day 1 (0.25, 0.75, and 2 hours post-dose); Day 5 (predose, 2.5, and 3.5 hours post-dose) | Cmax is defined as maximum plasma concentration of GS-441524, the active metabolite of obeldesivir. |
| PK Parameter: Ctrough of GS-441524, Metabolite of Obeldesivir | Day 5: Predose | Ctrough is defined as the trough observed drug concentration \[measured concentration at predose of Day 5 (taken directly before next administration)\]. |
| Change From Baseline in RSV Nasal Swab Viral Load at Day 5 | Baseline, Day 5 | Nasal swab samples was used to assess RSV viral load by reversetranscriptase-quantitative polymerase chain reaction (RT-qPCR), respiratory coinfection by multiplex respiratory pathogen PCR, potential infectious viral titer assessment, and potential resistance testing (by sequencing and/or phenotyping). Baseline was defined as the last available value collected on or prior to first dose of study drug. |
| Time to Sustained Alleviation of Targeted RSV Symptoms by Day 28 | Up to Day 28 | Sustained alleviation of targeted RSV symptoms was defined as 3 daily consecutive assessments (48-hour period) with improvement in score by at least 1 point for any targeted RSV symptom with baseline score is \> 1; or no increase in score for any targeted RSV symptom with baseline score of 1, assessed from Day 1 to Day 28. The time to sustained alleviation of targeted RSV symptoms by Day 28 was calculated as the symptom alleviation date minus the first dose date. Targeted RSV symptoms referred to the RSV symptoms (cough, respiratory signs, RSV signs, behavior impact). |
| Time to Resolution of Targeted RSV Symptoms by Day 28 | Up to Day 28 | Resolution of targeted RSV symptoms was defined as: for 2 daily consecutive assessments, improvement in score resulting in score of ≤2 for any targeted RSV symptom with baseline score \>2; no increase or an improvement in score resulting in score of ≤2 for any targeted RSV symptom with baseline score of 2; no increase in score for any targeted RSV symptom with baseline score of 1. The time to resolution of targeted RSV symptoms by Day 28 was calculated as the resolution date/time minus the first dose date/time. Targeted RSV symptoms referred to RSV symptoms (cough, respiratory signs, RSV signs, behavior impact). |
| Number of Participants With Palatability Questionnaire Response as Assessed by the Caregiver at Days 1 and 5 | Days 1 and 5 | Caregivers were asked to rate how the study drug tasted to their child. A questionnaire was administered to caregivers to assess palatability. Palatability was assessed by caregivers using a questionnaire on Day 1 and Day 5 with response options: Super Good, Good, Maybe Good or Maybe Bad, Bad, or Super Bad. |
| Number of Participants With Acceptability Questionnaire Response as Assessed by the Caregiver at Days 1 and 5 | Days 1 and 5 | Caregivers were asked to evaluate how easy it was for children to take the study drug. A questionnaire was administered to caregivers to assess acceptability. Acceptability was assessed by caregivers using a questionnaire with response options: Super Easy, Easy, Maybe Easy or Maybe Hard, Hard, or Super Hard. The questionnaire evaluated how easy it was for children to take the study drug. |
Countries
Japan, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
7 participants were screened. The study was terminated early after 4 participants were enrolled. The decision was not based on any safety findings. The study was planned to include Cohort 1 Part A (inclusive of 4 groups based on participant's weight), Cohort 1 Part B, and Cohort 2. Due to the early termination, only Cohort 1 Part A (Groups 2 and 3) were enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 17 months STANDARD_DEVIATION 20.8 |
| Age, Customized ≥ 2 to < 5 years | 0 Participants |
| Age, Customized < 2 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 1 / 2 | 0 / 1 |
Outcome results
None listed