Boceprevir in HIV-HCV Coinfected Patients Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The majority of Human immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) co-infected patients are non responders after 48 weeks of the current standard-of-care with Peg-Interferon/Ribavirin. The results of re-treatment are disappointing. The addition of Boceprevir to the current standard-of-care has been shown to increase the efficacy of therapy in HCV mono-infected patients previously treated with a bi-therapy. Knowing that HIV/HCV co-infected patients are subject to more rapid hepatic fibrosis as well as to increased risks of cirrhosis, end-stage liver disease and hepatocellular carcinoma, it is important to improve the response rate of the re-treatment of hepatitis C in these patients.

The aim of this pilot study is to evaluate the efficacy and safety of Boceprevir in combination with Peg-Interferon alfa 2b plus ribavirin, in patients co-infected with HIV and chronic genotype 1 HCV, and previously treated with Peg-Interferon/Ribavirin. 80 subjects will be enrolled. The primary endpoint will be the Sustained Virologic Response (SVR) defined as undetectable HCV-RNA at Week 24 after the end of therapy.

• 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)
• Collaborators: Merck Sharp & Dohme Corp.; Rennes University Hospital
• Treatments: Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2b; Ribavirin

Criteria

Inclusion Criteria:

• Adult ≥18 years

• HIV-1 infection

• Infection to genotype 1 HCV only

• Patients must have received at least 12 weeks of treatment with Peg-Interferon alfa 2a ≥ 135 µg / once weekly or Peg-Interferon alfa 2b ≥ 1,0 µg/kg/ once weekly + Ribavirin ≥ 600 mg daily and must have failed to treatment.

• Anti-HCV treatment stopped for at least 6 months

• Patients must be already treated at screen since at least 3 months with a stable combination of antiretroviral treatment as following:

• Either tenofovir - emtricitabine, and atazanavir in combination with ritonavir

• Or tenofovir - emtricitabine, and raltegravir

• If patients cannot receive neither of the two antiretroviral regimens proposed, for virologic, safety or toxicity reasons, patients could receive any effective antiretroviral therapy including : tenofovir, emtricitabine, lamivudine, atazanavir alone or in combination with ritonavir, raltegravir, abacavir. These patients are not allowed to take part in the pharmacokinetic sub-study.

• CD4 > 200/mm3 et >15%, at screen

• HIV-RNA < 50 copies/ml since at least 6 months at screen

• ≥ 40 Kg and ≤ 125 Kg

• Patients with any fibrosis grade. Proportion of F4 subjects should not excess 50% of the overall subjects.

• Male and female subjects must agree to use acceptable methods of contraception 1 month prior to starting the study treatment and to continue until 7 months after the last doses of study drugs for male subjects and their partner(s), 4 months for female subjects.

• Subjects must be willing to give written informed consent for principal study (signed at least at screen visit and prior to any study investigation)and + for the pharmacokinetic sub-study (for the concerned centers).

• Subjects must be willing to give written informed consent for biological collection.

• Subjects must be willing to give written informed consent for treatment of genetics data.

• Subjects affiliated or beneficiary to a medical insurance.

Exclusion Criteria:

History:

• Patients with cirrhosis (F4) and nul responders to prior treatment

• Cirrhosis classified Child-Pugh B or C or history of decompensated cirrhosis of the liver. If Child A classification, significant varicose veins (grade 2 or 3) observed with a fibroscopy realized for < 3 years.

• History of ocular neuritis, retinal disorders, transplant

• Opportunistic infections (classification C), active or occurred within the 6 months prior to baseline.

• History of neoplasia within the last 5 years, except cutaneous basocellular carcinoma, recovering Kaposi's sarcoma, in situ cervical or anal canal cancer.

Current condition:

• Co-infection with Hepatitis B virus

• Pregnancy and lactation

• Cardiac or severe pulmonary disease

• Untreated dysthyroidism

• Autoimmune disease contraindicating to an interferon treatment

• Severe haemoglobinopathies

• Any condition needing a systemic corticotherapy or an immunosuppressive treatment

• Evolutive current malignancy, including hepatocarcinoma which should be specifically controlled prior to baseline.

• Alcohol consumption which may disturb the study participation according to the investigator

• Drug addiction which may disturb the study participation according to the investigator. Patients taking part to a substitution program with methadone or buprenorphine are allowed to be enrolled in the study.

Biological criteria:

• Haemoglobin < 12 g/dL (female) or < 13g/dL (male), Platelets < 90 000/mm3, Neutrophil count < 1500/mm3, Renal failure defined as creatinine clearance < 50ml/min, Uncontrolled thyroid function, HbA1c ≥ 7% in case of diabetes

Criteria related to study drugs

• Contra-indication to Ribavirin, interferon treatment including psychiatric contra-indications.

• History of discontinuation for intolerance to anti-HCV treatment.Patients with a history of discontinuation for intolerance, especially anaemia or leuconeutropenia, and who were not treated with hematopoietic growth factor, are eligible

• Concomitant medication which may interfere with Boceprevir, atazanavir, ritonavir and raltegravir pharmacokinetic

• St.John's-wort consumption