A Phase 2, Open-Label, Multicenter, Multi-cohort, Single-Arm Study to Investigate the Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 106
- 主要终点
- For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF)
研究概览
简要总结
This study will have two parts as follows:
The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir (SOF) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety and tolerability of 7 days of dosing of SOF+ribavirin (RBV) in HCV-infected pediatric participants.
The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate SOF dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of SOF+RBV for 12 or 24 weeks in pediatric participants with genotype 2 or 3 HCV infection, respectively.
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 genotype 2 or 3
- •Screening laboratory values within defined thresholds
- •PK Lead-in only: all individuals must be treatment naive
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 HIV, acute hepatitis A virus, or hepatitis B virus
- •Clinical hepatic decompensation (ie, 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, SOF+RBV 12 Weeks (GT 2)
Participants between 12 to < 18 years of age with genotype (GT) 2 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
干预措施: SOF (Drug)
12 to < 18 Years Old, SOF+RBV 12 Weeks (GT 2)
Participants between 12 to < 18 years of age with genotype (GT) 2 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
干预措施: RBV (Drug)
12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 12 to < 18 years of age with genotype 3 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
干预措施: SOF (Drug)
12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 12 to < 18 years of age with genotype 3 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
干预措施: RBV (Drug)
6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2)
Participants between 6 to < 12 years of age with genotype 2 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
干预措施: SOF (Drug)
6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2)
Participants between 6 to < 12 years of age with genotype 2 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
干预措施: RBV (Drug)
6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 6 to < 12 years of age with genotype 3 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
干预措施: SOF (Drug)
6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 6 to < 12 years of age with genotype 3 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
干预措施: RBV (Drug)
3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2)
Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 12 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 12 weeks.
干预措施: SOF (Drug)
3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2)
Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 12 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 12 weeks.
干预措施: RBV (Drug)
3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 24 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 24 weeks.
干预措施: SOF (Drug)
3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3)
Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 24 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 24 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)
时间窗: 6 to < 18 years of age: predose, 0.5, 1, 2, 3, 4, 8, and 12 hours postdose on Day 7; 3 to < 6 years of age: predose, 2, 4, 8, and 12 hours postdose on Day 7
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
For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)
时间窗: Posttreatment Week 12
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
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, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only))
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase(Up to Day 7)
- 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 24 Weeks After Discontinuation of Therapy (SVR24)(Posttreatment Week 24)
- 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, 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 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 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, 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)
- For the Treatment Phase, Palatability of SOF Granules at Day 1 as Assessed by the Percentage of Participants Able/Unable to Taste the SOF Oral Granules(Day 1)