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

Phase 4CompletedNCT01925183

Markus Peck-Radosavljevic6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis C, Chronic HIV

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Proportion of Subjects With Sustained Virologic Response (SVR12)

Defined as HCV-RNA negativity by a sensitive assay

Time frame: Follow-up week 12 (FU12)

Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Baseline (BL) to Follow-up week 12 (FU12)