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.

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