A Prospective, Phase III, Open-Label Study of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in HCV/HIV Coinfected Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 262
- 试验地点
- 43
- 主要终点
- Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)
研究概览
简要总结
Hepatitis C virus (HCV) infection is a leading cause of death and illness in people with HIV-1. At the time the study was designed, the standard treatment for people with HIV-1 and HCV coinfection included two drugs: pegylated-interferon alfa 2b (PEG-IFN) and ribavirin (RBV). The purpose of this study was to evaluate the effectiveness of giving boceprevir (BOC) together with standard treatment in treating HCV infection in people with HIV-1 and HCV coinfection.
详细描述
For HIV-1-infected individuals, HCV infection is a leading cause of morbidity and mortality, and the prevalence of HCV infection is higher among those infected with HIV-1. At the time the study was designed, the standard-of-care (SOC) therapy for HCV infection was treatment with both PEG-IFN and RBV. This therapy is 40%-45% effective in patients with HCV infection but is significantly less effective in patients with both HCV and HIV-1 (Shire et al. J Viral Hepat., 2007). The purpose of this study was to evaluate the effectiveness of adding BOC (Kwo et al. Lancet, 2010), an HCV protease inhibitor, to SOC therapy in treating HCV infection (genotype 1) in HCV/HIV-1-coinfected adults.
Participants were enrolled into one of two groups based on previous HCV treatment experience.
- Group A: HCV treatment-naive participants who had never received treatment with PEG-IFN or experimental agents used to treat HCV, with or without RBV (N=170, refer to the note below).
- Group B: HCV treatment-experienced participants who had received any treatment with standard interferon or with PEG-IFN with or without RBV, provided the last dose of treatment was 90 days or more before study entry (N=140, refer to the note below).
Note: The team correspondence with the FDA led to an amendment to close enrollment in December 2013, prior to the target sample sizes of 170 in Group A and 140 in Group B, as the study power could be lowered while still meeting the key study objectives.
All participants had to be on stable antiretroviral therapy (ART) for at least 8 weeks prior to study entry using a dual nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone plus one of the following: efavirenz (EFV), raltegravir (RAL), lopinavir (LPV)/ritonavir (RTV) 400/100 mg twice daily, atazanavir (ATV)/RTV, darunavir (DRV)/RTV 600/100 mg twice daily OR must not have received any ART for at least 4 weeks immediately prior to entry. Participation in this study lasted approximately 72 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
HCV Treatment-Naive (Group A)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Pegylated-Interferon Alfa 2b (PEG-IFN) (Drug)
HCV Treatment-Naive (Group A)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Ribavirin (RBV) (Drug)
HCV Treatment-Naive (Group A)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Boceprevir (BOC) (Drug)
HCV Treatment-Experienced (Group B)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Pegylated-Interferon Alfa 2b (PEG-IFN) (Drug)
HCV Treatment-Experienced (Group B)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Ribavirin (RBV) (Drug)
HCV Treatment-Experienced (Group B)
Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
干预措施: Boceprevir (BOC) (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)
时间窗: 24 weeks after treatment discontinuation
SVR24 was defined as undetectable HCV RNA (below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0) at 24 weeks after treatment discontinuation. Participants without HCV RNA for SVR24 determination were considered not to have achieved SVR24.
次要结局
- Percentage of Participants With HIV-1 Viral Load <50 Copies/mL(Entry and weeks (W) 4, 8, 12, 24, 28, 40, 48, 52, 60, 72)
- Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)(From study treatment dispensation to Week 72)
- CD4+ T-Cell Count (CD4) Change From Baseline(Entry and weeks (W) 8, 12, 24, 28, 40, 48, 52, 60, 72)
- Number of Participants With Undetectable HCV RNA at Week 4, 8 and 12 Study Visits(Weeks (W) 4, 8, 12)
- Number of Participants With Grade 2 or Higher Signs and Symptoms and Laboratory Abnormalities and Other Serious AEs(From study treatment dispensation to Week 28)
- Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12)(12 weeks after treatment discontinuation)
- Number of Participants With Undetectable HCV RNA at Week 16, 20, 24 and 28 Study Visits(Weeks (W) 16, 20, 24, and 28)