Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in Asiatic HCV Patients Resistant to Bitherapy

Study Overview
=================
Brief 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 Asiatic patients with Hepatitis C chronic infection identified as non responders to the standard bi-therapy alone.

Detailed Description
-----------------
This is a Phase I/IIa inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in Asiatic adult patients infected by virus of genotype 1 of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (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 one subcutaneous administration of CYT107 per week for a total of 4. Groups of 3 to 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
-----------------
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
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: Interleukin-7


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: HCV Genotype 1 infected patients Absence of viral response to previous treatments with pegylated interferon-alpha plus ribavirin Metavir ≤ F3 assessed by biopsy in the last 12 months Main Exclusion Criteria: Active 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 Other liver disease Body mass index (BMI) > 30kg/m2 Relapse after previous response to pegylated IFN alpha and ribavirin therapy Previous bi-therapy with pegylated IFN alpha and ribavirin not well tolerated (in particular treatment discontinuation) 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 Inability to give informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>* 3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin in Asian patients with a chronic infection by a genotype 1 HCV not responding to this combination therapy |  | 12 weeks after start of CYT107 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and pharmacodynamics of CYT107 in this patients population. |  | At short and mid terms follow-ups | 
| potential anti-viral effect of CYT107 |  | 4 weeks and 12 weeks after start of CYT107 | 
| long-term safety and viral load variations |  | 24 and 48 weeks after the start of CYT107 | 
| immune specific response to HCV |  | 8 and 12 weeks after start of CYT107 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
interleukin-7, immune-based therapies, hepatitis C, chronic hepatitis, resistance to Peg-interferon and ribavirin bitherapy, immune specific responses to HCV, taiwan, phase 1/2a, viral disease, liver disease