A Phase IIa, Randomized, Double-blind (Participant and Investigator Blind, Sponsor Open), Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Antiviral Activity of Oral ACH-0141625 in Combination With Pegylated Interferon Alpha-2a and Ribavirin in Two Segments, After 28 Days of Dosing and, Subsequently, After 12 Weeks of Dosing in Participants With Chronic Hepatitis C Virus Genotype 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Segment 2: Complete Early Virologic Response (cEVR)
研究概览
简要总结
Evaluate safety, tolerability, and antiviral response of ACH-0141625 compared to standard of care in hepatitis C virus (HCV)-positive participants.
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
- •Males and females, aged 18 years and older
- •Chronic hepatitis C genotype 1 (as specified in the protocol)
- •Treatment naive
- •Females who are post-menopausal and amenorrheic must have a follicle-stimulating hormone (FSH) at screening. Females of childbearing potential must have a negative pregnancy test at screening and baseline. Females must use a non-hormonal method of contraception and must agree not to get pregnant during the study and for 6 months following the discontinuation of standard of care (SOC).
- •Fertile males must agree to use a condom and his female partner must agree to use 1 or more methods of contraception. Males must not donate sperm during the study and 3 months following the last exposure to RBV.
排除标准
- •Body mass index (BMI) >36 kilograms (kg)/square meter (m^2)
- •Pregnant or nursing females or females of childbearing potential not willing to comply with contraceptive measures per protocol. Men whose female partners are pregnant or contemplating pregnancy. - Coinfection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV)
- •Other significant diseases including liver disease
- •History of drug or alcohol dependence or addiction within the past 6 months
- •History of participation in a clinical trial with a protease inhibitor or previous treatment with a protease inhibitor, where at least 1 dose of the protease inhibitor was consumed.
- •Use of herbal or homeopathic products, illicit drugs, cytochrome P450 (CYP) 3A4/5 substrates, inducers or inhibitors, hormonal methods of contraception, corticosteroids, immunosuppressive, or cytotoxic agents within 28 days of the first dose of study drug.
- •Have a clinically significant laboratory abnormality at screening (as specified in the protocol).
- •Segment 1: Participants with any history of decompensated liver disease defined as cirrhotic participants with a Child-Pugh score of > or = to
- •Segment 2: Participants who have had a liver biopsy that shows bridging fibrosis or cirrhosis.
- •Nonalcoholic steatohepatitis if ballooning degeneration or Mallory bodies are present on liver biopsy.
- •Participants who prematurely discontinued, interrupted, or dose reduced prior Peg-IFN and RBV therapy due to noncompliance or safety issues.
- •Encephalopathy or altered mental status of any etiology.
- •History of moderate, severe, or uncontrolled psychiatric disease (as specified in the protocol).
- •History of malignancy of any organ system treated or untreated within the past 5 years.
- •Use of colony stimulating factor agents within 90 days prior to baseline.
- •History of seizure disorder.
- •History of known coagulopathy including hemophilia.
- •Clinically of significant findings on fundoscopic or retinal examination at screening
- •History of immunologically mediate disease.
- •History of clinical evidence of chronic cardiac disease (as specified in the protocol)
- •Received concomitant systemic antibiotic, antifungals, or antivirals for the treatment of active infection within 14 days prior to the first dose of the study drug (as specified in the protocol)
研究组 & 干预措施
Segment 2: 200 mg ACH-0141625
200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 2 : 800 mg ACH-0141625
800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 1: 400 mg ACH-0141625
400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 1: 200 milligrams (mg) ACH-0141625
200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 1: 200 milligrams (mg) ACH-0141625
200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 1: 200 milligrams (mg) ACH-0141625
200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
干预措施: Ribavirin (Drug)
Segment 1: 400 mg ACH-0141625
400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 1: 400 mg ACH-0141625
400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Ribavirin (Drug)
Segment 1: 800 mg ACH-0141625
800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 1: 800 mg ACH-0141625
800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 1: 800 mg ACH-0141625
800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Ribavirin (Drug)
Segment 1: Placebo
Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Placebo (Drug)
Segment 1: Placebo
Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 1: Placebo
Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
干预措施: Ribavirin (Drug)
Segment 2: 200 mg ACH-0141625
200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 2: 200 mg ACH-0141625
200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Ribavirin (Drug)
Segment 2 : 400 mg ACH-0141625
400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: ACH-0141625 (Sovaprevir) (Drug)
Segment 2 : 400 mg ACH-0141625
400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 2 : 400 mg ACH-0141625
400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Ribavirin (Drug)
Segment 2 : 800 mg ACH-0141625
800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Pegylated Interferon alpha-2a (Drug)
Segment 2 : 800 mg ACH-0141625
800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
干预措施: Ribavirin (Drug)
结局指标
主要结局
Segment 2: Complete Early Virologic Response (cEVR)
时间窗: Week 12
The primary efficacy endpoint for Segment 2 of the study was the percentage of participants achieving cEVR, defined as undetectable HCV RNA at Week 12.
Segment 1: Rapid Viral Response At Week 4 (RVR4)
时间窗: 4 weeks
The primary efficacy endpoint for Segment 1 of the study was the percentage of participants in each treatment group achieving RVR4 (hepatitis C virus \[HCV\] ribonucleic acid (RNA) less than or equal to the limit of quantitation \[LOQ\] at the Week 4 visit).
Segment 2: Safety
时间窗: 12 weeks
Segment 2: Percentage of participants with the following: adverse events, abnormal laboratory safety tests and dose reductions, interruptions and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Segment 1: Safety
时间窗: 4 weeks
Segment 1: Percentage of participants with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening Division of AIDS (Acquired Immunodeficiency Syndrome) (DAIDs) graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
次要结局
- Segment 1: cEVR(12 weeks)
- Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24)(6 months post-dosing)
- Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12)(3 months post-dosing)
- Segment 1 And Segment 2: End Of Treatment Response(Week 48 (Segment 1); Week 24 (Segment 2))
- Segment 1 And Segment 2: HCV RNA Change From Baseline(Week 12)
- Segment 2: RVR4(4 weeks)