Hepatitis C
Conditions
Keywords
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
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 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 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
Interventions
DRUGInterleukin-7
3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week
Sponsors
Cytheris SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
France, Italy, Switzerland
Outcome results
None listed