Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C (HIVCOBOC-RGT)

Markus Peck-Radosavljevic

Status and phase: Completed; Phase 4

Conditions: Hepatitis C, Chronic; HIV

Treatments: Drug: Boceprevir; Drug: Ribavirin; Drug: Pegylated interferon alpha-2a

Study type: Interventional

Funder types: Other

Identifiers

NCT01925183

2012-005591-33 (EudraCT Number)

HIVCOBOC-RGT

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

6 participants in 2 patient groups

28 weeks of treatment duration

Experimental group

Description:

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.

Treatment:

Drug: Pegylated interferon alpha-2a

Drug: Ribavirin

Drug: Boceprevir

48 weeks of treatment duration

Experimental group

Description:

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

Treatment:

Drug: Pegylated interferon alpha-2a

Drug: Ribavirin

Drug: Boceprevir