Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C

Study Overview
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Brief Summary
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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.

Official Title
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Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients

Conditions
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Hepatitis C, Chronic, HIV

Intervention / Treatment
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* Drug: Pegylated interferon alpha-2a
* Drug: Ribavirin
* Drug: Boceprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: HCV-GT other than HCV-GT 1. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 28 weeks of treatment duration<br>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. | Drug: Pegylated interferon alpha-2a<br>* 180mcg once weekly; subcutaneous injection<br>* Other names: Pegasys®, Roche;Drug: Ribavirin<br>* 600mg two times daily (BID) (e.g. 3x200mg at 6am, 3x200mg at 6pm) in patients ≥75kg body weight; 2x200mg at 6am and 3x200mg at 6pm in patients <75kg; orally<br>* Other names: Copegus®, Roche;Drug: Boceprevir<br>* 800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally<br>* Other names: Victrelis®, MSD;|
| Experimental: 48 weeks of treatment duration<br>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 | Drug: Pegylated interferon alpha-2a<br>* 180mcg once weekly; subcutaneous injection<br>* Other names: Pegasys®, Roche;Drug: Ribavirin<br>* 600mg two times daily (BID) (e.g. 3x200mg at 6am, 3x200mg at 6pm) in patients ≥75kg body weight; 2x200mg at 6am and 3x200mg at 6pm in patients <75kg; orally<br>* Other names: Copegus®, Roche;Drug: Boceprevir<br>* 800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally<br>* Other names: Victrelis®, MSD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Sustained Virologic Response (SVR12) | Defined as HCV-RNA negativity by a sensitive assay | Follow-up week 12 (FU12) | 
| Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Baseline (BL) to Follow-up week 12 (FU12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Boceprevir, HIV/HCV-coinfection, HIV/HCV coinfection, HIV/HCV, Response-guided therapy