A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Subjects Who Have Failed Prior Treatment With Pegylated Interferon and Ribavirin (P/R) With Chronic HCV GT1, GT4, and GT6 Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 420
- 主要终点
- Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12)
研究概览
简要总结
This is an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) with or without ribavirin (RBV) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infections who have failed prior therapy with pegylated interferon and RBV. The primary study hypothesis is that in at least one of the study arms, the percentage of participants achieving sustained viral response 12 weeks after the end of all study treatment (SVR12) will be superior to 58%.
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
- 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
- •Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typable or mixed genotype infection (positive for anti-HCV antibody, HCV ribonucleic acid [RNA], or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
- •Cirrhosis defined as liver biopsy showing METAVIR F4; or Fibroscan showing result >12.5 kilopascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST):platelet ratio index (APRI) of >2
- •Absence of cirrhosis defined as liver biopsy showing absence of cirrhosis; or Fibroscan result of ≤ 12.5 kPa; or Fibrosure® (Fibrotest®) score of ≤ 0.48 and APRI ≤ 1
- •Previous HCV treatment status of peginterferon/RBV Null responder; or peginterferon/RBV Partial responder; or peginterferon/RBV Treatment Relapse
- •For human immunodeficiency virus (HIV) co-infected participants: documented HIV-1 infection; currently naïve to treatment with any antiretroviral therapy (ART) and have no plans to initiate ART treatment while participating in this study; or be on HIV ART for at least 8 weeks prior to study entry (dual nucleoside reverse transcriptase inhibitor [NRTI] backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) (no changes in HIV regimen allowed within 4 weeks of randomization); cluster of differentiation 4 (CD4)+ T-cell count >200 cells/mm^3 at screening; documented undetectable plasma HIV-1 RNA at least 8 weeks prior to screening; participants not on ART, HIV RNA must be <50,000 copies/mL; must have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance
- •Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; a male participant who is not (or whose partner is not) of reproductive potential is eligible without requiring the use of contraception
排除标准
- •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
- •For participants with cirrhosis, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded
- •Co-infected with hepatitis B virus
- •Has had previous direct-acting antiviral treatment
- •History of malignancy <=5 years prior 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 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
- •Taking or plans to take any HIV therapy that includes a ritonavir-boosted or unboosted protease inhibitor, efavirenz or etravirine
- •Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
- •Clinically-relevant drug or alcohol abuse within 12 months
- •Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; or is a male whose female partner(s) is/are pregnant
- •History of organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
- •Poor venous access
- •History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
- •Hemoglobinopathy, including, but not limited to, thalassemia major
- •Any medical condition requiring, or likely to require, chronic systemic corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial
- •For participants with HIV, history of opportunistic infection in the preceding 6 months
- •For participants with HIV, use of HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine)
- •Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
研究组 & 干预措施
Grazoprevir + Elbasvir 12 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg fixed-dose combination (FDC) tablets once daily (q.d.) by mouth for 12 weeks.
干预措施: Grazoprevir + Elbasvir (Drug)
Grazoprevir + Elbasvir + RBV 12 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules twice daily (b.i.d.) by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.
干预措施: Grazoprevir + Elbasvir (Drug)
Grazoprevir + Elbasvir + RBV 12 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules twice daily (b.i.d.) by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.
干预措施: Ribavirin (Drug)
Grazoprevir + Elbasvir 16 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.
干预措施: Grazoprevir + Elbasvir (Drug)
Grazoprevir + Elbasvir + RBV 16 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
干预措施: Grazoprevir + Elbasvir (Drug)
Grazoprevir + Elbasvir + RBV 16 weeks
Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
干预措施: Ribavirin (Drug)
结局指标
主要结局
Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12)
时间窗: 12 weeks after the end of all study treatment (up to 28 weeks)
HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Experiencing Adverse Events (AE)
时间窗: Up to 18 weeks
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Discontinuing Study Treatment Due to an AE
时间窗: Up to 16 weeks
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
次要结局
- Percentage of Participants Achieving Undetectable HCV RNA 24 Weeks After the End of All Treatment (SVR24)(24 weeks after the end of all study treatment (up to 40 weeks))