Clinical trial NCT01925183: Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C
Official title: Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
HIV
Keywords: Boceprevir
HIV/HCV-coinfection
HIV/HCV coinfection
HIV/HCV
Response-guided therapy
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
First posted: 2013-08-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Subjects With Sustained Virologic Response (SVR12)
timeFrame: Follow-up week 12 (FU12)
measure: Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline (BL) to Follow-up week 12 (FU12)
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna
Study officials:
affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna
name: Markus Peck-Radosavljevic, MD
role: PRINCIPAL_INVESTIGATOR
References: