A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection and Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 237
- 主要终点
- Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
研究概览
简要总结
This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)
- •Evidence or no evidence of liver cirrhosis based on one of the following:
- •Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)
- •Fibroscan performed within 12 months of Day 1 of this study
- •Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period)
- •Has HCV status that is one of the following:
- •Treatment naïve
- •Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)
- •Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen
- •Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
- •Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations
排除标准
- •Evidence of decompensated liver disease
- •On peritoneal dialysis for management of kidney disease
- •Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
- •History of malignancy <=5 years prior to signing informed consent
- •Clinical diagnosis of substance abuse
- •Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations
- •Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
- •Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
- •Uncontrolled or poorly controlled hypertension
- •Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent
- •New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent
- •Severe active peripheral vascular disease
- •Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
- •Evidence or history of chronic hepatitis not caused by HCV
研究组 & 干预措施
Immediate Treatment
Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.
干预措施: Grazoprevir (Drug)
Immediate Treatment
Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.
干预措施: Elbasvir (Drug)
Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
干预措施: Grazoprevir (Drug)
Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
干预措施: Elbasvir (Drug)
Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
干预措施: Placebo to Grazoprevir (Drug)
Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
干预措施: Placebo to Elbasvir (Drug)
Intensive PK
Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
干预措施: Grazoprevir (Drug)
Intensive PK
Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
干预措施: Elbasvir (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
时间窗: Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period
时间窗: Up to Week 12
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods
时间窗: Up to Week 14
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
次要结局
- Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)(Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment))
- Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)(Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment))