Telaprevir in HIV-HCV Coinfected Patients Who Had Previously Failed a Peginterferon-Ribavirin Regimen

• Status: Completed
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase II, multicentric, national pilot trial is designed to estimate the sustained virological response rate (SVR) following a 12 weeks treatment by telaprevir combined with a 48 or 72 weeks treatment by peginterferon and ribavirin, based upon the rapid virological response (RVR) at week 8 (4 weeks after telaprevir start), and to compare the observed SVR to 20%, a rate determining a significant therapeutic benefit in this population of patients. The primary endpoint will be the SVR defined as undetectable HCV-RNA measured 24 weeks after the end of therapy (EOT).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborator: Janssen-Cilag Ltd.
• Treatments: Interferon-alpha; Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• Informed consent form signed at screening visit at the latest

• Patient registered with or covered by a social security scheme

• HIV-1 infection

• Chronic, genotype 1, hepatitis C with detectable HCV RNA at screening

• Virological failure following a previous treatment of at least 12 weeks by peginterferon alpha-2a ≥ 135 µg once weekly or peginterferon alpha-2b ≥ 1.0 µg per kg once weekly + ribavirin ≥ 600 mg once daily. Virological failure defined by persistence of a detectable HCV-RNA, with the same genotype than before. Null responder patient, with less than 2 Log10 HCV-RNA decline at week 12 with cirrhosis are excluded from the study. Null responder patients without cirrhosis (equal or below METAVIR F3) are limited to less than 30 % of all patients included

• No Interferon and/or Ribavirin within past 6 months

• Stable antiretroviral treatment for over 3 months at screening. Authorized combinations: tenofovir-emtricitabine-boosted atazanavir,tenofovir-emtricitabine-efavirenz,tenofovir-emtricitabine-raltegravir, once Drug-Drug interaction data will be available. Patients with a stable combination of at least 3 of the following drugs: tenofovir, emtricitabine/lamivudine, efavirenz, atazanavir-boosted or not, raltegravir. These patients cannot participate in the pharmacokinetic study

• CD4 >200/mm3 and >15% at screening

• Plasma HIV-RNA <50 copies/mL for at least 6 months at screening visit

• Body weight ≥ 40 kg to equal or below 125 kg

• Fibrosis stage have to be documented by a significant liver biopsy (cumulative length ≥ 15 mm or ≥ 6 portal spaces), within 3 years. Patients with a previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4) are allowed to enter the study without a new biopsy. The proportion of patients with cirrhosis lesions (METAVIR F4) is limited to 50% of all patients.

• Male patients, female patients with child-bearing potency and their heterosexual partners must use an adequate contraception from 1 month before initiation of treatment to 7 months following the end of treatment for men and to 4 months following the end of treatment for women. Subjects (or their female partners) must not be pregnant or planning to become pregnant within 2 years after enrolling in the study

Exclusion Criteria:

• Patient with liver failure (Child B and C) or past history of decompensated cirrhosis

• Significant oesophageal varices (Stages 2-3) on a gastrointestinal endoscopy within 3 years

• Detectable AgHBs

• HIV-2 co-infection

• Contra-indication to ribavirin or peginterferon

• Severe pre-existing cardiac or pulmonary disease

• Untreated dysthyroidism

• Uncontrolled Type 2 diabetes

• Optic neuritis past history and retinal condition

• History of organ transplant

• Severe hemoglobinopathy

• Congenital QT prolongation, family history of congenital QT prolongation or sudden unexpected death

• Contra-indication to telaprevir, hypersensitivity to any component of the drug product

• Any disease requiring long term, systemic corticotherapy or immunosuppressive therapy during study

• Alcohol intake that may represent an obstacle for the participation of the subject

• Substance abuse that may represent an obstacle for the participation of the subject

• Acute CDC stage C opportunistic infection within the previous 6 months

• Past history of cancer within the previous 5 years (except skin basal cell carcinoma, Kaposi's disease in stable remission, in situ cervical cancer and in situ anal cancer)

• Any active malignant disease including hepatocellular carcinoma

• Patients unable to observe the study procedures

• Participation to another clinical trial within the previous 30 days

• Haemoglobin <120 g/L for women and <130 g/L for men

• Platelets <90 000/mm3

• Neutrophils <1 500/mm3

• Renal insufficiency defined by an estimated Glomerular Filtration Rate < 60 mL/mn (MDRD equation)

• Associated medication susceptible to interfere with the pharmacokinetic parameters of telaprevir and/or antiretroviral associated drugs