A Phase II, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682 + MK-8408 in Subjects With Chronic HCV Genotype 1, 2, 3, 4, 5 or 6 Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 160
- 主要终点
- Percentage of Participants Withdrawing From Study Therapy Due to an AE
研究概览
简要总结
This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. The impact of the study treatment regimen on the percentage of participants with undetectable HCV ribonucleic acid [RNA] 12 weeks after completing study treatment (SVR12) will be evaluated.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has hepatitis C virus (HCV) ribonucleic acid (RNA) at the time of screening
- •Has documented chronic HCV genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection
- •Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening
- •Has absence of cirrhosis or has compensated cirrhosis
- •Is HCV treatment-naïve or has experienced virologic failure after completing a prior interferon-containing regimen
- •Is of non-childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug
- •For human immunodeficiency virus (HIV) co-infected participants: is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study Or has well-controlled HIV on ART
排除标准
- •Is mentally or legally incapacitated, has significant emotional problems (at screening or expected during the study) or has a history of a clinically significant psychiatric disorder that would interfere with the study procedures.
- •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 Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score >6 if cirrhotic
- •Is co-infected with Hepatitis B Virus
- •Has a history of opportunistic infection in the preceding 6 months prior to screening if co-infected with HIV
- •Has a history of malignancy ≤5 years prior to study start (except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ) or is under evaluation for other active or suspected malignancy
- •Has cirrhosis and liver imaging within 6 months prior to study start showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
- •Is taking any medications or herbal supplements restricted by the study entry criteria in the period from ≤2 weeks prior to study start through 2 weeks after the last dose of study drug
- •Has clinically-relevant drug or alcohol abuse within 12 months of study start
- •Has participated in any clinical study of an investigational product within 30 days prior to the first dose of study drug
- •Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to study start and 14 days after the last dose of study drug
- •Is male and is expecting to donate sperm from at least 2 weeks prior to Day 1 until 14 days after the last dose of study drug
- •Has or has had any of the following: organ transplants (including hematopoietic stem cell transplants) other than cornea and hair; poor venous access; history of gastric surgery; or history of malabsorption disorders
- •Has any cardiac abnormalities/dysfunction including but not limited to: unstable angina; unstable congestive heart failure; or unstable arrhythmia
- •Has a history of a medical/surgical condition that resulted in hospitalization within 3 months prior to study start, other than for minor elective procedures
- •Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the study
- •Has evidence of history of chronic hepatitis not caused by HCV
研究组 & 干预措施
GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT2 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT1 Arm is sub-divided into GT1a and GT1b Arms. GT1a Arm will enroll approximately 35 participants including up to 10 participants who are compensated cirrhotics and GT1b Arm will enroll approximately 15 participants including up to 5 participants who are compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT1 Arm is sub-divided into GT1a and GT1b Arms. GT1a Arm will enroll approximately 35 participants including up to 10 participants who are compensated cirrhotics and GT1b Arm will enroll approximately 15 participants including up to 5 participants who are compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT2 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT3 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT3 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT4 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT4 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT5 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT5 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT6 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
干预措施: Uprifosbuvir 450 mg (Drug)
GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg
Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT6 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
干预措施: Ruzasvir 60 mg (Drug)
结局指标
主要结局
Percentage of Participants Withdrawing From Study Therapy Due to an AE
时间窗: Up to Week 12
The percentage of participants discontinuing from study therapy during the treatment period was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of Participants With ≥1 Events of Clinical Interest (ECIs)
时间窗: Up to Week 14 (up to 2 weeks after completing study therapy)
The percentage of participants with ECIs was determined. ECIs were defined as the following: 1) an overdose of study drug; 2) first instance of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>500 IU/L; 3) first instance of ALT or AST \>3x nadir and \>3x upper limit of normal (ULN); 4) first instance of estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2; or 4) first instance of serum creatinine \>1.3x ULN and elevated from baseline.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
时间窗: Week 24 (12 weeks after completing study therapy)
The percentage of participants in each arm achieving SVR12 was determined. SVR12 was defined as HCV ribonucleic acid (RNA) levels in plasma \< lower limit of quantification (LLOQ) 12 weeks after completing study treatment. Plasma levels of HCV RNA were measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
Percentage of Participants With ≥1 Adverse Events (AEs)
时间窗: Up to Week 14 (up to 2 weeks after completing study therapy)
The percentage of participants experiencing an AE during the treatment period and first 2 weeks of follow-up was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)(Week 36 (24 weeks after completing study therapy))
- Percentage of Participants With Virologic Failure (VF)(12 weeks after the end of all study therapy (24 weeks))
- Percentage of Participants With Baseline Resistance-Associated Substitutions (RAS) Achieving SVR12(12 weeks after the end of all study therapy (24 weeks))