Clinical trial NCT03820258: Study to Investigate Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) Fixed Dose Combination (FDC) in Adolescents and Children With Chronic Hepatitis C Virus (HCV) Infection
Official title: A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed Dose Combination in Adolescents and Children With Chronic HCV Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatitis C Virus Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-01-29
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the steady-state pharmacokinetics (PK) and confirm the age-appropriate dose of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection.

Detailed description: Participants will receive placebo to match SOF/VEL/VOX FDC to assess ability to swallow tablets at screening up to Day 1.

Eligibility criteria: Key Inclusion Criteria:

* Consent of parent or legal guardian required
* Chronic HCV infection
* Screening laboratory values within defined thresholds
* Individuals must have a determination of prior treatment status:

  * DAA-naive is defined as either:

    * Treatment naive with no prior exposure to any interferon (IFN), ribavirin (RBV), or approved or experimental HCV-specific DAA
    * Treatment experienced with an IFN-based regimen and no prior exposure to an approved or experimental HCV-specific DAA
  * DAA-experienced is defined as prior exposure to a regimen including any DAA (eg, non-structural protein (NS)3/4A protease inhibitor, NS5A inhibitor, or NS5B nucleotide/nucleoside inhibitor)

Key Exclusion Criteria:

* History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
* Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV) or hepatitis B virus (HBV)
* Clinical hepatic decompensation (eg, clinical ascites, encephalopathy, and/or variceal hemorrhage)
* Pregnant or nursing females
* Known hypersensitivity to study medication
* Use of any prohibited concomitant medications as within 28 days of the Day 1 visit

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX
timeFrame: Sparse PK Sample (all participants): At Weeks 1 and 8 at any time, Weeks 2 and 4 (predose and between 15 minutes and 4 hours postdose). Intensive PK Sample [PK Substudy (N=14)]: Week 2 or Week 4 (0 (predose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose)
Secondary outcomes:
measure: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
timeFrame: First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants With HCV RNA < LLOQ 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With HCV RNA < LLOQ 24 Weeks After Discontinuation of Therapy (SVR24)
timeFrame: Posttreatment Week 24
measure: Percentage of Participants With Overall Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: Percentage of Participants With HCV RNA < LLOQ on Treatment
timeFrame: Weeks 1, 2, 4, and 8
measure: Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX During Treatment
timeFrame: Up to End of Treatment (Week 8)
measure: Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX When Treatment is Discontinued
timeFrame: Up to Posttreatment Week 24
measure: Change in HCV RNA From Day 1 Through End of Treatment
timeFrame: Baseline (Day 1); Weeks 1, 2 ,4, and 8
measure: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
timeFrame: Baseline (Day 1); Week 1, 2, 4, 8, and Posttreatment/Follow-up Week 4 (FU-4)
measure: Change From Baseline in Height Percentiles as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, Posttreatment/Follow-up Week 12 (FU-12), and Posttreatment/Follow-up Week 24 (FU-24)
measure: Change From Baseline in Weight Percentiles as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, FU-12, and FU-24
measure: Number of Participants by Tanner Stage Assessment as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); Weeks 8, FU-12, and FU-24
measure: Change From Baseline in Radiographic Bone Age Assessment as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); Week 8
measure: Change From Baseline in C-Type Collagen Sequence (CTX) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); FU-24
measure: Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development
timeFrame: Baseline (Day 1); FU-24
measure: Percentage of Participants in Each Swallowability Category of Able to Swallow or Unable to Swallow SOF/VEL/VOX 400/100/100 mg Size Tablets
timeFrame: Baseline (Day 1)
measure: Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Study Participant
timeFrame: Baseline (Day 1); Week 8
measure: Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Parent/Legal Guardian
timeFrame: Week 8
measure: Neuropsychiatric Assessments Based on Questionnaire as Completed by Participant
timeFrame: Weeks 8, FU-12, and FU-24
measure: Neuropsychiatric Assessments Based on Questionnaire as Completed by Parent/Legal Guardian
timeFrame: Weeks 8, FU-12, and FU-24
measure: Change From Baseline in Neuropsychiatric Assessments as Completed by Participant
timeFrame: Baseline (Day 1); Weeks 8, FU-12, and FU-24
measure: Change From Baseline in Neuropsychiatric Assessments as Completed by Parent/Legal Guardian
timeFrame: Baseline (Day 1); Weeks 8, FU-12, and FU-24
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: SOS-intraSOC Epatologia
city: Milano
country: Italy
facility: US Infettivologia Pediatrica-Polo Universitario
city: Milan
country: Italy
facility: Servizio di Epatologia e Nutrizione Pediatrica
city: Napoli
country: Italy
facility: UOS Epatologia Pediatrica
city: San Giovanni Rotondo
country: Italy
facility: UOSD Epatologia
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital
city: Poznan
country: Poland
facility: Med Polonia
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im.
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings Healthcare NHS Trust Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: