Pilot Study to Assess the Efficacy of and Tolerance to a QUadruple Therapy to Treat HIV-HCV Coinfected Patients Previously Null Responders

• Status: Completed
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Evaluation of efficacy and tolerance to a QUadruple therapy with Asunaprevir , Daclatasvir, Ribavirin and pegylated Interferon alpha-2a, in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a standard Pegylated Interferon -Ribavirin regimen.

The proportion of patients presenting cirrhosis (defined by a METAVIR F4 score on liver biopsy and/or with hepatic impulse elastometry ≥ 15 kPa) will be limited to 50% of all of the patients included

• 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: Bristol-Myers Squibb
• Treatments: Asunaprevir; Interferon-alpha; Interferons; Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• Adult ≥18 years with confirmed HIV-1 or 2 infection

• Infection with HCV genotype 1 or 4 only, confirmed and with detectable HCV-RNA ≥ 1000 IU/mL at screening.

• Null responders to a previous treatment with Peginterferon and Ribavirin, defined by a fall of less than 2 log10 IU/ml HCV-RNA from baseline to week 12.

• Stable antiretroviral treatment for > 1 month at screening containing any of the following drugs: Raltegravir, Enfuvirtide, Tenofovir-Emtricitabine, Abacavir-Lamivudine.

• CD4 > 200 /mm3 and > 15% at screening

• HIV-RNA < 400 copies/mL from ≥ 3 months at screening

• Any liver fibrosis stage,

• with the assessment of the presence or not of cirrhosis at screening:

• previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4), and/or

• significant liver biopsy (cumulative length ≥ 15 mm and ≥ 6 portal spaces), within 18 months and after the end of last HCV treatment, and/or

• significant and reliable liver stiffness assessment (Fibroscan®) within 6 months (at least 10 measures with IQR less then 25% of the mean value and a success rate of at least 80%)

• cirrhosis being defined as a METAVIR score F4 on liver biopsy and/or liver elastometry ≥ 15 kPa

• the proportion of patients with cirrhosis (METAVIR F4) is limited to 50% of all patients.

• Body weight ≥ 40 kg and ≤125 kg

• Male patients, female patients with child-bearing potential and their heterosexual partners must use 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.

• Informed and signed consent

• For participating patients, informed and signed consent for the pharmacokinetic sub-study

• Patients affiliated to the National Health Insurance or covered by Universal Medical Coverage

• For the first 12 patients included (who will participate to the pharmacological substudy): stable antiretroviral treatment for > 1 month at screening, with Raltegravir+ Emtricitabine+ Tenofovir

Exclusion Criteria:

• CHILD B and C cirrhosis, past history of decompensated cirrhosis. Patients with CHILD A cirrhosis must demonstrate the absence of significant oesophageal varices (Stages 2-3) on an upper gastrointestinal endoscopy ≤ 12 months

• Positive HBs antigenemia with HBV DNA > 1000 IU/ml((if positive AgHBs with HBV DNA ≤ 1000 IU/mL, patient will be included provided it is treated with Ténofovir)

• Pregnant women, breast-feeding women

• Refusal of adequate contraception

• Contra-indication to Ribavirin, including hypersensitivity reaction to Ribavirin

• Contra-indication to Peginterferon, including psychiatric contra-indications. Patients with significant psychiatric past history, notably severe depression requiring hospitalization or suicide attempt, cannot be included unless they undergo a psychiatric evaluation and obtain a specific authorization for the use of interferon.

• Premature discontinuation (during the first six months) of a previous HCV treatment for toxicity. Patients who have stopped a previous treatment for severe anaemia or neutropenia can enter the study if erythropoietin or granulocyte growth factor had not been used during the previous treatment

• Previous HCV therapy including HCV NS3 protease inhibitor

• Severe pre-existing cardiac or pulmonary disease

• History of organ transplant

• Acute CDC stage C opportunistic infection occurring within the previouW6 months

• Any active malignant disease including hepatocellular carcinoma for which a specific assessment is required at screening

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

• Substance abuse that may represent an obstacle for the participation of the subject in the study. Stabilized patients included in a substitution program can participate in the study

• Patients with previous observance problem unable to observe the study procedures

• Participation in another clinical trial within the previous 30 days

• Haemoglobin < 90 g/L

• Platelets < 50 000 /mm3

• Neutrophil count < 750 /mm3

• Renal insufficiency defined by an estimated Glomerular Filtration Rate < 50 mL/mn (MDRD equation)

• Absence of antiretroviral treatment or antiretroviral treatment different from the authorized combinations

• Associated medication likely to interfere with any of the study drugs such as CPY3A4 inducers (rifampin, Millepertuis)