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, viral disease, liver disease
Brief summary
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
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.
Interventions
DRUGInterleukin-7
4dose levels: 3, 10, 20 and 30µg/kg. 4 administrations, 1 per week
Sponsors
Cytheris SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
France, Italy, Switzerland
Outcome results
None listed