A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 226
- 主要终点
- For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF
研究概览
简要总结
The primary objective of the PK Lead-in Phase of the study is to evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.
The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The primary objective of the Treatment Phase is to evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.
During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
排除标准
- •History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol.
- •Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
- •Clinical hepatic decompensation (i.e., ascites, encephalopathy 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
12 to < 18 Years Old
Participants between 12 to < 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: LDV/SOF (Drug)
12 to < 18 Years Old
Participants between 12 to < 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: RBV (Drug)
6 to < 12 Years Old
Participants between 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: LDV/SOF (Drug)
6 to < 12 Years Old
Participants between 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: RBV (Drug)
3 to < 6 Years Old
Participants between 3 to < 6 years of age weighing ≥ 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing < 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: LDV/SOF (Drug)
3 to < 6 Years Old
Participants between 3 to < 6 years of age weighing ≥ 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing < 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets).
Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.
United Kingdom:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks
United States/Australia/New Zealand:
- HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
- HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
- HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
干预措施: RBV (Drug)
结局指标
主要结局
For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF
时间窗: Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase
时间窗: Up to 24 weeks
次要结局
- For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA(Baseline; Weeks 1, 2, 4, 8, and 12)
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase(Up to Day 10)
- For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)(Posttreatment Week 12)
- For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair(Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24)
- For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development(Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24)
- For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair(Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24)
- For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)(Posttreatment Week 24)
- For the Treatment Phase, Change From Baseline in HCV RNA(Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only))
- For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment(Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only))
- For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough(Up to 24 weeks)
- For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse(Up to Posttreatment Week 24)
- For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization(Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4)
- For the Treatment Phase, Change From Baseline in Height(Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24)
- For the Treatment Phase, Change From Baseline in Weight(Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24)
- For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development(Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24)
- Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1(Day 1)
- Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1(Day 1)