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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 10
- 主要终点
- Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX
研究概览
简要总结
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.
详细描述
Participants will receive placebo to match SOF/VEL/VOX FDC to assess ability to swallow tablets at screening up to Day 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Experimental: Cohort 1 (12 to < 18 years old), 8 Weeks
Direct-acting antiviral (DAA)-naive participants without cirrhosis in Cohort 1 (12 to < 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 8 weeks.
干预措施: SOF/VEL/VOX (Drug)
Experimental: Cohort 1 (12 to < 18 years old), 12 Weeks
DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 1 (12 to < 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 12 weeks.
干预措施: SOF/VEL/VOX (Drug)
Experimental: Cohort 2 (6 to < 12 years old), 8 Weeks
DAA-naive participants without cirrhosis in Cohort 2 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.
干预措施: SOF/VEL/VOX (Drug)
Experimental: Cohort 2 (6 to < 12 years old), 12 Weeks
DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 2 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 12 weeks.
干预措施: SOF/VEL/VOX (Drug)
Experimental: Cohort 3 (3 to < 6 years old), 8 Weeks
DAA-naive participants without cirrhosis in Cohort 3 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.
干预措施: SOF/VEL/VOX (Drug)
Experimental: Cohort 3 (3 to < 6 years old), 12 Weeks
DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 3 (3 to < 6 years old) will receive SOF/VEL/VOX FDC for 12 weeks.
干预措施: SOF/VEL/VOX (Drug)
结局指标
主要结局
Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX
时间窗: 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)
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For participants with separate consent to participate in the optional intensive PK substudy, intensive serial PK blood samples were collected at Week 2 or Week 4. Sparse PK samples were collected from all participants at Weeks 1, 2, 4, and end of treatment/Week 8. Plasma concentration data from all PK samples (intensive and sparse) were combined and used to generate PK parameters of SOF, GS-331007, VEL, and VOX for all participants using a population PK modeling approach.
次要结局
- Neuropsychiatric Assessments Based on Questionnaire as Completed by Parent/Legal Guardian(Weeks 8, FU-12, and FU-24)
- Change From Baseline in Neuropsychiatric Assessments as Completed by Participant(Baseline (Day 1); Weeks 8, FU-12, and FU-24)
- Change From Baseline in Neuropsychiatric Assessments as Completed by Parent/Legal Guardian(Baseline (Day 1); Weeks 8, FU-12, and FU-24)
- Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event(First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days)
- Percentage of Participants With HCV RNA < LLOQ 24 Weeks After Discontinuation of Therapy (SVR24)(Posttreatment Week 24)
- Change in HCV RNA From Day 1 Through End of Treatment(Baseline (Day 1); Weeks 1, 2 ,4, and 8)
- Change From Baseline in Radiographic Bone Age Assessment as a Measurement of Growth and Development(Baseline (Day 1); Week 8)
- Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)(Posttreatment Week 12)
- Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX When Treatment is Discontinued(Up to Posttreatment Week 24)
- Change From Baseline in Weight Percentiles as a Measurement of Growth and Development(Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, FU-12, and FU-24)
- Percentage of Participants With HCV RNA < LLOQ 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- Percentage of Participants With Overall Virologic Failure(Up to Posttreatment Week 24)
- Percentage of Participants With HCV RNA < LLOQ on Treatment(Weeks 1, 2, 4, and 8)
- Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development(Baseline (Day 1); FU-24)
- Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX During Treatment(Up to End of Treatment (Week 8))
- Percentage of Participants With Alanine Aminotransferase (ALT) Normalization(Baseline (Day 1); Week 1, 2, 4, 8, and Posttreatment/Follow-up Week 4 (FU-4))
- Percentage of Participants in Each Swallowability Category of Able to Swallow or Unable to Swallow SOF/VEL/VOX 400/100/100 mg Size Tablets(Baseline (Day 1))
- Change From Baseline in Height Percentiles as a Measurement of Growth and Development(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))
- Number of Participants by Tanner Stage Assessment as a Measurement of Growth and Development(Baseline (Day 1); Weeks 8, FU-12, and FU-24)
- Change From Baseline in C-Type Collagen Sequence (CTX) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development(Baseline (Day 1); FU-24)
- Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Study Participant(Baseline (Day 1); Week 8)
- Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Parent/Legal Guardian(Week 8)
- Neuropsychiatric Assessments Based on Questionnaire as Completed by Participant(Weeks 8, FU-12, and FU-24)