A Phase IIb Clinical Study to Assess the Pharmacokinetics, Safety, and Efficacy of the Combination Regimen of Elbasvir (EBR)/Grazoprevir (GZR) in Participants Aged 3 to Less Than 18 Years With Chronic Hepatitis C Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 15
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics (PK), safety, and efficacy of oral MK-5172 (a fixed dose combination [FDC] tablet containing elbasvir [EBR] 50 mg and grazoprevir [GZR] 100 mg) and EBR/GZR (varying doses) pediatric granules in pediatric hepatitis C virus (HCV)-infected participants who are 3 to <18 years of age. Within each age cohort (Cohort 1: 12 to <18 years of age; Cohort 2: 7 to <12 years of age; and Cohort 3: 3 to <7 years of age), a Mini Cohort of 7 participants will be enrolled first. For the oldest cohort (Cohort 1), the Mini Cohort will assess ability to swallow a placebo tablet prior to administering active FDC tablets; participants in Cohorts 2 and 3 will take pediatric granules instead of a tablet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Has documented chronic HCV genotype (GT) 1 or GT4 infection
- •Has the following liver disease staging assessment: absence of cirrhosis or compensated cirrhosis
- •Has one of the following HCV treatment statuses:
- •GT1 and GT4: treatment-naïve (TN), defined as no prior exposure to any interferon (IFN)-containing regimen, ribavirin (RBV), or other HCV-specific direct acting antiviral (DAA) agent
- •GT1 only: treatment-experienced (TE) with no previous treatment with HCV specific DAA agents.
- •If female is not pregnant, not breastfeeding, and is either not of childbearing potential or follows the contraceptive guidance during the treatment period and for at least 14 days after the last dose of study treatment.
排除标准
- •Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of advanced liver disease.
- •Is cirrhotic AND has a Child-Turcotte-Pugh score >6, corresponding to a Child Class B or C.
- •Is co-infected with Human Immunodeficiency Virus (HIV).
- •Has evidence of past or present hepatitis B infection.
- •Has a history of malignancy ≤5 years prior to signing informed consent or is under evaluation for other active or suspected malignancy.
- •Female expects to conceive or donate eggs from Day 1 through at least 14 days after the last dose of study treatment or longer.
- •Has any of the following conditions: organ transplants other than cornea and hair; poor venous access; history of gastric surgery or malabsorption disorders; any clinically significant cardiac abnormalities/dysfunction that may interfere with participant treatment, assessment, or compliance; any major medical condition which might interfere with participant treatment, assessment, or compliance; history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment; medical/surgical conditions that may result in a need for hospitalization during the study duration; any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor antagonists, or immunosuppressant drugs; life-threatening serious adverse event (SAE) during the screening period; history of chronic hepatitis not caused by HCV.
- •If female has a positive urine pregnancy test within 24 hours before the first dose of study treatment.
- •Is taking or plans to take prohibited medications, or is taking herbal supplements.
- •Has had previous HCV direct acting antiviral (DAA) treatment.
- •Is currently participating or has participated in a study with an investigational compound within prior 30 days
- •Has significant emotional problems or a clinically significant psychiatric disorder that may interfere with participant treatment, assessment, or compliance with the protocol.
- •Has clinically relevant drug or alcohol abuse within prior 12 months that may interfere with participant treatment, assessment, or compliance.
研究组 & 干预措施
EBR/GZR
Pediatric participants receive EBR/GZR as either FDC tablets or oral granules once daily for 12 weeks. A 24-week follow-up period will follow the 12-week treatment regimen.
干预措施: EBR/GZR FDC Tablet (Drug)
EBR/GZR
Pediatric participants receive EBR/GZR as either FDC tablets or oral granules once daily for 12 weeks. A 24-week follow-up period will follow the 12-week treatment regimen.
干预措施: Placebo (Drug)
EBR/GZR
Pediatric participants receive EBR/GZR as either FDC tablets or oral granules once daily for 12 weeks. A 24-week follow-up period will follow the 12-week treatment regimen.
干预措施: Grazoprevir Oral Granules (Drug)
EBR/GZR
Pediatric participants receive EBR/GZR as either FDC tablets or oral granules once daily for 12 weeks. A 24-week follow-up period will follow the 12-week treatment regimen.
干预措施: Elbasvir Oral Granules (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The AUC0-24hr of EBR at steady state (Week 4) was determined in each cohort.
Steady State Predose Drug Concentration (Ctrough) of EBR
时间窗: Week 4: Predose
The Ctrough of EBR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
Maximum Plasma Concentration (Cmax) of EBR
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The Cmax of EBR at steady state (Week 4) was determined in each cohort.
AUC0-24hr of GZR at Steady State
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The AUC0-24hr of GZR at steady state (Week 4) was determined in each cohort.
Ctrough of GZR
时间窗: Week 4: Predose
The Ctrough of GZR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
CL/F of GZR at Steady State
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The CL/F of GZR at steady state (Week 4) was determined in each cohort.
Apparent Clearance (CL/F) of EBR at Steady State
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The CL/F of EBR at steady state (Week 4) was determined in each cohort.
Cmax of GZR
时间窗: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
The Cmax of GZR at steady state (Week 4) was determined in each cohort.
次要结局
- Percentage of Participants With ≥1 Adverse Event (AE)(Up to 36 weeks)
- Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)(Week 24)
- Percentage of Participants Discontinuing Study Treatment Due to an AE(Up to 12 weeks)