A Safety and Efficacy Study of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 765
- 主要终点
- Number of Participants With Sustained Virologic Response (SVR)
研究概览
简要总结
This was an open-label, randomized safety and efficacy trial in adult, treatment-naïve Chronic Hepatitis C (CHC) participants with genotype 1 infection. The study conducted in 2 parts, compared standard-of-care PegIntron (1.5 μg/kg, once weekly [QW]), plus ribavirin (800 to 1400 mg/day), for 48 weeks to five treatment paradigms containing boceprevir (SCH 503034) 800 mg thrice a day (TID). The five treatments included boceprevir (BOC) plus standard-of-care for 28 or 48 weeks, with and without a 4-week lead-in with PegIntron (PEG) and ribavirin (RBV), and exploration of PegIntron plus low-dose ribavirin (400 to 1000 mg/day) plus boceprevir for 48 weeks.
详细描述
The study was conducted in 2 parts.
Part 1 of the study had 5 arms using weight based ribavirin 800-1400 mg/day and compared:
- PegIntron and ribavirin for 48 weeks (Arm 1 - Control)
- PegIntron, ribavirin, and boceprevir for 28 weeks (Arm 2)
- Lead-in with PegIntron and ribavirin for 4 weeks followed by PegIntron, ribavirin and boceprevir for 24 weeks (Arm 3)
- PegIntron, ribavirin and boceprevir for 48 weeks (Arm 4)
- Lead-in with PegIntron and ribavirin for 4 weeks, followed by PegIntron, ribavirin and boceprevir for 44 weeks (Arm 5)
Participants from Arm 1 receiving PegIntron and ribavirin that were HCV positive after 24 weeks of treatment had the option to receive boceprevir in combination with PegIntron and ribavirin for an additional 24 weeks. All participants from Arm 1 that started boceprevir after Week 24 formed the crossover arm (Arm 8).
Part 2 of the study assessed the safety and efficacy of low dose ribavirin (400-1000 mg/day) and compared:
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 60 years;
- •Body weight between 45 and 125 kg;
- •Documented chronic hepatitis C genotype 1;
- •Liver biopsy with histology consistent with chronic hepatitis and no other etiology for chronic liver disease within of 5 years of Day 1;
- •Participant and participant's partner(s) must each agree to use acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months after the last dose of study medication;
- •Written informed consent.
排除标准
- •Include, but are not limited to, the following:
- •Prior treatment for hepatitis C;
- •Co-infection with HIV or hepatitis B virus (HBsAg positive);
- •Evidence of decompensated liver disease;
- •Diabetic and hypertensive participants with clinically significant ocular exam findings;
- •Pre-existing psychiatric condition, including but not limited to:
- •Current moderate or severe depression;
- •History of depression associated with any of the following:
- •Hospitalization for depression;
- •Electroconvulsive therapy for depression;
- •Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions;
- •Suicidal or homicidal ideation and/or attempt;
- •History of severe psychiatric disorders (including but not limited to schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder or mania);
- •Past history or current use of lithium;
- •Past history or current use of antipsychotic drugs for listed conditions.
- •Substance abuse within protocol specified timeframes;
- •Pre-existing medical conditions that could interfere with the participant's participation in and completion of the study, including but not limited to chronic pulmonary disease, cardiac dysfunction or immunologically-mediated disease;
- •Active or suspected malignancy or history of malignancy within the past 5 years;
- •Participants who are pregnant or nursing; participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
- •Treatment with any investigational drug or participation in any clinical trial 30 days within Screening;
- •Hemoglobin <12 g/dL for females and <13 g/dL for males;
- •Neutrophils <1500 mm^3; Blacks: <1200/mm^3;
- •Platelets <100,000/mm^3;
- •Other clinically significant laboratory test abnormalities.
研究组 & 干预措施
Arm 1. PEG +RBV for 48 Wks (Part I)
Participants treated with PegIntron (1.5 μg/kg, once weekly [QW]) and Ribavirin (800 to 1400 mg/day) for 48 weeks.
Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron (1.5 μg/kg, QW), Ribavirin (800 to 1400 mg/day), and boceprevir (800 mg three times daily [TID]) for 24 additional weeks. The participants that crossed over to receive boceprevir formed Arm 8. The total treatment duration was up to 54 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 1. PEG +RBV for 48 Wks (Part I)
Participants treated with PegIntron (1.5 μg/kg, once weekly [QW]) and Ribavirin (800 to 1400 mg/day) for 48 weeks.
Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron (1.5 μg/kg, QW), Ribavirin (800 to 1400 mg/day), and boceprevir (800 mg three times daily [TID]) for 24 additional weeks. The participants that crossed over to receive boceprevir formed Arm 8. The total treatment duration was up to 54 weeks.
干预措施: ribavirin (Drug)
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
干预措施: ribavirin (Drug)
Arm 3. PEG + RBV + BOC (from Wk 4) for 24 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 3. PEG + RBV + BOC (from Wk 4) for 24 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 3. PEG + RBV + BOC (from Wk 4) for 24 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
干预措施: ribavirin (Drug)
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)
Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
干预措施: ribavirin (Drug)
Arm 5. PEG + RBV + BOC (from Wk 4) for 44 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 5. PEG + RBV + BOC (from Wk 4) for 44 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 5. PEG + RBV + BOC (from Wk 4) for 44 Wks (Part I)
Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
干预措施: ribavirin (Drug)
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: ribavirin (Drug)
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), low-dose ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks (Arm 7) during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), low-dose ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks (Arm 7) during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Participants receiving PegIntron (1.5 μg/kg QW), low-dose ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks (Arm 7) during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.
干预措施: ribavirin (low-dose) (Drug)
Arm 8. PEG + RBV + BOC (from Wk 24) for 48 Wks (Part I)
Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with
PegIntron (1.5 μg/kg QW), and ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.
干预措施: boceprevir (SCH 503034) (Drug)
Arm 8. PEG + RBV + BOC (from Wk 24) for 48 Wks (Part I)
Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with
PegIntron (1.5 μg/kg QW), and ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.
干预措施: peginterferon-alfa 2b (PegIntron) (Drug)
Arm 8. PEG + RBV + BOC (from Wk 24) for 48 Wks (Part I)
Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with
PegIntron (1.5 μg/kg QW), and ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.
干预措施: ribavirin (Drug)
结局指标
主要结局
Number of Participants With Sustained Virologic Response (SVR)
时间窗: From follow-up week (FW) 24 up to end of follow-up (EOF)
Participants with undetectable HCV-RNA at FW 24 up to EOF had achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with reverse-transcriptase-polymerase chain reaction (RT-PCR) assay, with a lower limit of detection (LLD) of 29 international units/mL (IU/mL). A participant in Arm 2 with undetectable HCV-RNA at FW 24 had detectable HCV-RNA after FW 24. He is not considered to achieve SVR.
次要结局
- Number of Participants With SVR Based on Duration of Boceprevir Treatment(From FW 24 up to EOF)
- Number of Participants Negative for HCV-RNA at FW 12(At FW 12)
- Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR(At FW 12 and FW 24 up to EOF)
- Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin(From FW 24 up to EOF)
- Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization(72 weeks post randomization)
- Number of Participants With an Early Virologic Response (EVR) That Achieved SVR(At TW 12, and at FW 24 up to EOF)
- Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR(At FW 24 up to EOF and at 72 weeks post randomization)