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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Interleukin-7


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYT107<br> | Drug: Interleukin-7<br>* 4dose levels: 3, 10, 20 and 30µg/kg. 4 administrations, 1 per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 8 weeks after start of CYT107 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and pharmacodynamics of CYT107 in this patients population. |  | As primary | 
| potential anti-viral effect of CYT107 |  | As primary | 
| immune specific response to HCV |  | As primary | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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