Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in HCV Genotype 1 or 4 Patients Resistant to Bitherapy Alone

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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A Phase I/IIa Dose Escalation Study of Repeated Administration of CYT107 (Glyco-r-hIL-7) Add-On Treatment in Genotype 1 or 4 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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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

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYT107<br> | Drug: Interleukin-7<br>* 3 dose levels: 3, 10 & 20 µg/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 |
| --- | --- | --- |
| To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin |  | 12 weeks after the start of IL-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize pharmacokinetics and pharmacodynamics of CYT107 |  | 12 weeks after the start of IL-7 | 
| To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107 |  | 12 weeks after the start of IL-7 | 
| To evaluate the immune specific response to HCV |  | 12 weeks after the start of IL-7 | 
| To document the long-term safety and viral load variations |  | 48 weeks after the start of IL-7 | 

 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 1/2a, viral disease, liver disease