PEG-Intron/REBETOL vs PEG-Intron/ SCH 503034 With and Without Ribavirin in Chronic Hepatitis C Virus Genotype 1 (HCV-1) Peginterferon Alfa/Ribavirin Nonresponders: A SCH 503034 Dose-Finding Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 357
- 主要终点
- Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT)
研究概览
简要总结
The primary objective of this study is to determine the safe and effective dose range of boceprevir (SCH 503034) in combination with PEG-Intron in adult subjects who have chronic hepatitis C without cirrhosis, and who have failed an adequate course of combination therapy with peginterferon-alfa plus ribavirin. A secondary objective is to explore whether ribavirin provides an additional benefit when combined with PEG-Intron plus boceprevir.
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
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1A: PegIntron (PEG) + Ribavirin (RBV)
A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is undetected, PEG + RBV will continue for another 36 weeks.
干预措施: PegIntron (PEG) (Biological)
Arm 1A: PegIntron (PEG) + Ribavirin (RBV)
A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is undetected, PEG + RBV will continue for another 36 weeks.
干预措施: Ribavirin (RBV) (Drug)
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Ribavirin (RBV) (Drug)
Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)
A single dose of PEG is given first, followed 1 week later by PEB + BOC 100 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)
A single dose of PEG is given first, followed 1 week later by PEB + BOC 100 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Ribavirin (RBV) (Drug)
Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)
A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800
By first protocol amendment to P03659, this non-randomized arm is added. A single dose of PEG is given first, followed 1 week later by PEG + BOC 800 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: Boceprevir (BOC) (Drug)
Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800
By first protocol amendment to P03659, this non-randomized arm is added. A single dose of PEG is given first, followed 1 week later by PEG + BOC 800 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.
干预措施: PegIntron (PEG) (Biological)
Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.
干预措施: Ribavirin (RBV) (Drug)
结局指标
主要结局
Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT)
时间窗: Baseline up to Week 49
Sustained Viral Response (SVR) was defined as the percentage of participants with HCV-RNA undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.
Percent of Participants Who Achieved Sustained Virologic Response (SVR)
时间窗: Baseline up to Week 73 [24 weeks after end of treatment (EoT)]
SVR was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.
次要结局
- Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA(Baseline up to Week 73 [24 weeks after EoT])
- Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop(Week 1 and Week 49)
- Percent of Participants With Virologic Response Prior to Amendment 2(Week 3, Week 5, Week 13)
- Peak Plasma Concentration of Boceprevir (BOC)(All visits during treatment (baseline to Week 49) except Day 1 of Week 1)
- Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period(All visits during treatment (baseline to Week 49) except Day 1 of Week 1)
- Trough Plasma Concentration Level(All visits during treatment (baseline to Week 49) except Day 1 of Week 1)
- Change in Alanine Aminotransferase (ALT) Levels(Baseline up to dosing change (> 25 weeks))
- Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on Arms 2 (PEG+BOC 100), 3 (PEG+BOC 200), 4 (PEG+BOC 400 [48 Weeks]), 6 (PEG+BOC 400 [24 Weeks])(From dosing change to end of follow-up (Week 73)(up to 48 weeks))
- Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Rebetol (RVB) + Boceprevir (BOC) 400 (Arm 5)(From dosing change to end of follow-up (Week 73)(up to 48 weeks))
- Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7)(From dosing change to end of follow-up (Week 73) (up to 48 weeks))