Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Proportion of Subjects With Sustained Virologic Response (SVR12)
研究概览
简要总结
Response-guided triple-therapy with boceprevir (BOC) in combination with pegylated interferon (PEGIFN) and ribavirin (RBV) is the current standard of care for HIV-negative patients infected with hepatitis C genotype (HCV-GT) 1. In contrast, in HIV-positive patients, a fixed treatment duration of 48 weeks is used.
The aim of this study is to assess efficacy and safety of response-guided triple-therapy with BOC in combination with PEGIFN and RBV in HIV-positive patients. Thus, treatment duration will be individualized based on HCV-RNA negativity at treatment week 8 (W8). All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at W8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks, while patients with detectable HCV-RNA at W8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed HIV infection (anti-HIV1/2 antibody positive).
- •Chronic HCV infection (anti-HCV positive, HCV-RNA detectable for >6 months).
- •HCV-GT 1 infection.
- •Age ≥18 years and ≤65 years.
- •No prior treatment with BOC/PEGIFN/RBV.
- •CD4+ cell count >200 cells/µL.
- •Stable antiretroviral therapy (ART) including tenofovir/emtricitabine (Truvada®, Gilead) and raltegravir (Isentress®, MSD) with HIV-RNA <50 copies/mL.
- •Valid result on transient elastography or liver biopsy within 6 months prior to enrollment.
- •Female patients of childbearing potential must agree to use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
- •Male patients or their female partners must agree to use an effective contraceptive during treatment and for 7 months after treatment has been concluded.
排除标准
- •HCV-GT other than HCV-GT
- •Cirrhotic patients (as defined by METAVIR F4 in liver biopsy or liver stiffness >12.3 kPa) with decompensated liver disease (Child-Pugh stage B/C).
- •Chronic liver diseases other than hepatitis C virus infection (hepatitis B virus infection: HBsAg positivity, nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cystic fibrosis).
- •Significant cardiac disease (ejection fraction <40% at echocardiography).
- •Significant pulmonary disease (COPD stage GOLD III/IV).
- •Significant renal disease (serum creatinine >1.5 mg/dL).
- •Subjects taking medication(s) that is/are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events such as but not limited to, orally administered midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine).
- •Contraindications for boceprevir (Victrelis®, MSD), pegylated interferon alpha-2a (Pegasys®, Roche) or ribavirin (Copegus®, Roche), as listed in section 4.3 of the respective summary of product characteristics (SmPCs).
- •Ongoing alcohol abuse (average daily alcohol consumption >50g).
- •Ongoing illicit drug abuse.
- •Unwillingness to give written informed consent.
- •Pregnancy and breastfeeding.
- •Women wishing to become pregnant.
研究组 & 干预措施
28 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at treatment week 8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks.
干预措施: Pegylated interferon alpha-2a (Drug)
28 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at treatment week 8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks.
干预措施: Ribavirin (Drug)
28 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at treatment week 8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks.
干预措施: Boceprevir (Drug)
48 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with detectable HCV-RNA at treatment week 8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks
干预措施: Pegylated interferon alpha-2a (Drug)
48 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with detectable HCV-RNA at treatment week 8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks
干预措施: Ribavirin (Drug)
48 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with detectable HCV-RNA at treatment week 8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks
干预措施: Boceprevir (Drug)
结局指标
主要结局
Proportion of Subjects With Sustained Virologic Response (SVR12)
时间窗: Follow-up week 12 (FU12)
Defined as HCV-RNA negativity by a sensitive assay
Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline (BL) to Follow-up week 12 (FU12)
次要结局
未报告次要终点
研究者
Markus Peck-Radosavljevic
Vice-chairman of the Division of Gastroenterology and Hepatology
Medical University of Vienna