Dose Escalation Study of IL-7 and Bi-therapy in HCV Patients Resistant After 12 Weeks of Bi-therapy (ECLIPSE 1) (ECLIPSE 1)

Dose Escalation Study of IL-7 and Bi-therapy in HCV Patients Resistant After 12 Weeks of Bi-therapy (ECLIPSE 1)

A PHASE I/IIa DOSE ESCALATION STUDY IN ASIA OF REPEATED ADMINISTRATION OF "CYT107" (Glyco-r-hIL-7) ADDED ON TREATMENT IN GENOTYPE 1 HCV INFECTED PATIENTS RESISTANT TO PEGYLATED INTERFERON-ALPHA AND RIBAVIRIN

This study will evaluate the safety of a new experimental drug, IL-7, in people with HCV infection resistant after 12 weeks of bi-therapy.

This is a Phase I inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in adult patients infected by Genotype 1 Virus of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (biotherapy)after 12 weeks of this standard bi-therapy. 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 a subcutaneous administration of CYT107 per week for a total of 4 administrations. Groups of 3 to 6 patients will be entered at each dose level of CYT107. Four dose levels are planned. Eligible patients will a cycle of four weekly injections at a defined dose level in addition to the bi-therapy. Standard bi-therapy will continue 4 weeks after CYT107 treatment discontinuation. The duration of study is approximately 11 weeks including screening period. Participants have 1 hospitalization overnight and 8 clinic visits. The four administrations are sub-cutaneous and are given as a shot under the skin in the arm or abdomen or leg. During the study visits the following may be done: Medical history, physical examination, blood tests every visit. Electrocardiogram (EKG) Chest x-ray study Liver/spleen imaging Blood sample collections at frequent intervals Urine tests several times during the study.

interleukin-7, immune-based therapies, hepatitis C, chronic hepatitis, resistance to Peg-interferon and ribavirin bi-therapy, immune specific responses to HCV, phase 1, viral disease, liver disease

Safety of biologically active doses of CYT107 added to a standard bi-therapy in patients with a chronic infection by a genotype 1 Hepatitis C Virus (HCV) not responding to this combination therapy 12 weeks after its initiation.

Main Inclusion Criteria: Genotype I infected patients Age > 18 years Absence of early viral response to a first treatment with PEG-interferon-alpha plus ribavirin given for at least 12 weeks. Absence of early viral response (EVR) will be defined as detectable HCV with a decrease HCV RNA load < 2 logs, measured by a quantitative PCR tests, as compared to baseline levels measured by a similar technique Ongoing treatment by PEG-interferon-alpha plus ribavirin at study entry Main Exclusion Criteria: Infection by HBV Infection by HIV-1 and /or HIV-2 Apart from HCV infection, presence of active infection requiring a specific treatment or a hospitalization Cirrhosis (Metavir F4) assessed by biopsy or FibroScan® or by liver biopsy within the last 6 months prior CYT107 treatment initiation. If assessed by Fibroscan® patients with a result > 10 KPa will be excluded Other liver disease (notably from alcoholic, metabolic or immunological origin) Body mass index (BMI) > 30kg/m2 Inability to give informed consent Administration of growth factors (G-CSF, EPO) within the 12 weeks of the combination therapy