Safety and Efficacy of Boceprevir in Combination With Peginterferon Plus Ribavirin for Treatment of Asia Pacific Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Pegylated Interferon Plus Ribavirin
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 282
- 主要终点
- Percentage of Participants in Korea and Taiwan With Sustained Virologic Response (SVR) at Follow-Up Week 24 - Full Analysis Set (FAS) Population
研究概览
简要总结
This study will assess the efficacy of boceprevir (BOC) in combination with PegIntron (pegylated interferon alfa-2b) (PEG) and ribavirin (RBV) in response guided therapy compared to the efficacy of standard-of-care therapy alone in adult subjects with chronic hepatitis C (CHC) genotype 1 who failed prior treatment with pegylated interferon and RBV in the Asia Pacific population. The primary hypothesis is that the proportion of participants achieving sustained virologic response in the experimental therapy regimen (BOC/PEG+RBV) is superior to that in the control arm (Placebo/PEG+RBV), in the Full Analysis Set (FAS) population.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Previously documented CHC genotype 1 infection. Other or mixed genotypes are not eligible.
- •Liver biopsy with histology consistent with CHC and no other etiology.
- •Participants with cirrhosis must have an ultrasound/imaging study within 6 months of screening (or between screening and Day 1) with no findings suspicious for hepatocellular carcinoma
- •Failed previous treatment (of at least 12 weeks) with pegylated interferon (alfa-2a or alfa-2b) plus RBV
- •Weight between 40 kg and 125 kg, inclusive
- •Of 'local' ancestral descent
- •Sexually active males and females of child-bearing potential must agree to use a medically accepted method of contraception
排除标准
- •Co-infected with the human immunodeficiency virus (HIV) or hepatitis B virus.
- •Required discontinuation of previous interferon or RBV regimen for an adverse event considered to be possibly or probably related to RBV and/or interferon.
- •Treatment with RBV within 90 days and any interferon-alpha within 1 month prior to screening.
- •Treatment for hepatitis C with any investigational medication or prior treatment with herbal remedies with known hepatotoxicity.
- •Treatment with any investigational drug or participation in any interventional clinical trial within 30 days of the screening visit.
- •Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
- •Diabetes and/or hypertension with clinically significant ocular examination findings.
- •Any condition the could interfere with participation in and completion of the trial.
- •Evidence of active or suspected malignancy, or history of malignancy within the last 5 years (except adequately treatment carcinoma in situ and basal cell carcinoma of the skin).
- •Pregnant or breast-feeding.
研究组 & 干预措施
Boceprevir
PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up.
干预措施: Boceprevir (BOC) (Drug)
Boceprevir
PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up.
干预措施: Placebo to boceprevir (Drug)
Boceprevir
PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up.
干预措施: Peginterferon alfa-2b (PEG) (Drug)
Boceprevir
PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up.
干预措施: Ribavirin (RBV) (Drug)
Control
PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14.
干预措施: Placebo to boceprevir (Drug)
Control
PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14.
干预措施: Peginterferon alfa-2b (PEG) (Drug)
Control
PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14.
干预措施: Ribavirin (RBV) (Drug)
Control
PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14.
干预措施: Cross-Over Boceprevir Treatment (Drug)
结局指标
主要结局
Percentage of Participants in Korea and Taiwan With Sustained Virologic Response (SVR) at Follow-Up Week 24 - Full Analysis Set (FAS) Population
时间窗: Follow-up Week 24
SVR is defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The last observation carried forward (LOCF) method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR.
Percentage of Participants in India With SVR at Follow-Up Week 24 - FAS Population
时间窗: Follow-up Week 24
SVR is defined as undetectable plasma HCV-RNA at FW24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The LOCF method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR.
次要结局
- Percentage of Participants in Korea and Taiwan With SVR at Follow-Up Week 24 - Modified Intent-to-Treat (mITT) Population(Follow-up Week 24)
- Percentage of Participants in India With SVR at Follow-Up Week 24 - mITT Population(Follow-up Week 24)
- Percentage of Participants in Korea and Taiwan Achieving Early Virologic Response (EVR) at Treatment Week 8(Treatment Week 8)
- Percentage of Participants in India Achieving EVR at Treatment Week 8(Treatment Week 8)
- Percentage of Participants With an Adverse Event (AE) of Anemia in Korea and Taiwan(Up to 96 weeks)
- Percentage of Participants With an AE of Anemia in India(Up to 96 weeks)
- Percentage of Participants With an AE of Neutropenia in Korea and Taiwan(Up to 96 weeks)
- Percentage of Participants With an AE of Neutropenia in India(Up to 96 weeks)