dose escalation study of interleukin-7 (il-7) and bitherapy in hcv genotype 1 or 4 patients resistant to bitherapy alone

Conditions: Hepatitis C

Summary: this study is designed to evaluate the safety of biological active dose of a new experimental drug, il-7, in combination with standard bi-therapy in patients with hepatitis c chronic infection identified as non responders to the standard bi-therapy alone.

this is a phase i/iia inter-patient dose-escalation study assessing weekly doses of interleukin-7 (cyt107) in adult patients infected by virus genotype 1 or 4 of hepatitis c and resistant to standard treatment with peg-interferon and ribavirin (bitherapy). the dose escalation is aimed at establishing the safety of a biologically active doses of cyt107 added to the combination therapy of pegylated interferon-alpha and ribavirin. at each dose level, study patients will receive one subcutaneous administration of cyt107 per week for a total of 4. groups of 6 patients will be entered at each dose level of cyt107. three dose levels are planned. eligible patients initially receive bi-therapy for 6-10 weeks. thereafter, cyt107 is added for a cycle of four weekly injections at a defined dose level while standard bi-therapy continues for 9 weeks after cyt107 treatment discontinuation. the patients are then followed on a regular basis until reaching 48 weeks after the cyt107 treatment. the duration of study is approximatively 60 weeks with 20-25 weeks of bi-therapy. participants will have 1 overnight hospitalization and 15 clinic visit on a period of 60 weeks. during the visits the following may be done: * medical history, physical examination, blood tests * electrocardiograms (ecg) * chest x-ray * liver/spleen imaging * urine tests

Eligibility criteria:
inclusion criteria: * genotype 1 or 4 infected patients * age \> 18 years * absence of viral response to previous treatments with pegylated interferon-alpha plus ribavirin defined as: * absence of early viral response (evr) with detectable hcv and with a decrease hcv rna load \< 2 logs, measured by a quantitative pcr tests after 12 weeks of treatment, as compared to baseline levels measured by a similar technique; or * absence of end of treatment response defined by detectable hcv rna at the end of treatment (24 weeks or 48 weeks) * metavir ≤ f3 assessed by biopsy in the last 12 months or by fibroscan if fibroscan® result \< 10 kpa in the last 6 months (biopsy can be avoided) exclusion criteria: * active infection by hbv (positive hbs ag or positive anti hbc antibodies with a detectable hbv dna viral load). * infection by hiv-1 and /or hiv-2 * apart from hcv infection, presence of active infection requiring a specific treatment or a hospitalization * other liver disease (notably from alcoholic, metabolic or immunological origin) * body mass index (bmi) \> 30kg/m2 * relapse after previous response to pegylated ifn alpha and ribavirin therapy * any history of malignancy apart from curatively treated basal cell carcinoma or in situ cervical carcinoma * history of clinical autoimmune disease or active auto-immune disease * history of severe asthma, presently on chronic medications * significant cardiac or pulmonary disease * prior solid organ or hematopoietic cell transplantation * dialyzed patient * inability to give informed consent

Keywords: interleukin-7 immune-based therapies hepatitis c chronic hepatitis resistance to peg-interferon and ribavirin bi-therapy immune specific responses to hcv phase 1/2a viral disease liver disease