Hepatitis C, genotypes 1 and 4 MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Sponsors
CYTHERIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Genotype 1 or 4 infected patients 2. Age > 18 years 3. 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 1500 / mm3 (or WBC > 3000/mm3) 8. Platelets > 100,000/ mm3 9. Hemoglobin normal 10. PT/PTT normal at screening 11. Normal creatinine 12. Normal TSH at screening 13. Normal alkaline phosphatase and conjugated bilirubin at screening. Increase in non conjugated bilirubin is tolerate in Gilbert’s syndrome or evidence of hemolysis 14. Appropriate social insurance Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Active infection by HBV (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load) 2. Infection by HIV-1 and /or HIV-2 3. Apart from HCV infection, presence of active infection requiring a specific treatment or a hospitalization 4. Other liver disease (notably from alcoholic, metabolic or immunological origin) 5. Body mass index (BMI) > 30kg/m2 6. ANA, SMA, anti LKM1, antithyroperoxydase or antimitochondrial antibodies with a titer > 1/80 in the 5 months preceding screening 7. Alpha-fetoprotein > 200 ng/mL or > 100 and 5 x ULN (grade 2) 9. Relapse after previous response to pegylated IFN alpha and ribavirin therapy 10. Previous bitherapy with pegylated IFN alpha and ribavirin not well tolerated (ex: EPO, GCSF, treatment discontinuation) that could be predictive of a non sufficient tolerance for a new bitherapy and CYT107 administration, in the judgment of the investigator 11. Any history of malignancy apart from curatively treated basal cell carcinoma or in situ cervical carcinoma 12. Clinical signs of mixed cryoglobulinemia 13. History of clinical autoimmune disease or active auto-immune disease 14. History of severe asthma, presently on chronic medications 15. Iron deficiencies 16. Significant cardiac or pulmonary disease 17. QTc prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities 18. Prior solid organ or hematopoietic cell transplantation 19. Dialyzed patient 20. Inability or refusal to practice an effective contraception until 6 months after the end of ribavirin treatment, in women of childbearing potential. Absence of protection until 6 months after the end of ribavirin treatment, in male patients or male partners of the patient. 21. Pregnancy or breastfeeding 22. History of medical or psychiatric disease which, in the view of the principal investigator, would preclude a good compliance 23. Current alcohol consumption 24. Current intravenous drug use 25. Concomitant treatment with anti-coagulant 26. Previous treatment with new antiviral drug under development (antipolymerase, antiprotease) at any time 27. Concomitant treatment or treatment within the previous 90 days prior to study entry by a drug known to have therapeutic activity in HCV infection or any immunomodulatory effect (apart from study drug), including systemic corticosteroids 28. Assessment of any other experimental therapy concomitantly or within the last 6 months. 29. Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin in patients with a chronic infection by a genotype 1 or 4 Hepatitis C Virus (HCV) not responding to this combination therapy (no EVR after 12 W or non SVR after 24 or 48 W);Secondary Objective: • To characterize pharmacokinetics and pharmacodynamics of CYT107. • To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107, after the completion of CYT107 treatment (W4) and 2 months after (W12). • To document the long-term safety and viral load variations at W24 and W48 post first CYT107 injection. • To study the evolutions of the CD3, CD4, CD8 and CD19 cells counts from baseline (before CYT107 administration) to W12 and long-term follow-up at W24 and W48. • To evaluate the immune specific response to HCV • To recommend a dose and administration schedule of CYT107, defining a basic cycle of treatment for phase IIb/IIIa development in patients with chronic HCV infections resistant to pegylated IFN-alpha and ribavirin therapy. ;Primary end point(s): 1. Tolerance criteria AE will be graded according to the CTC severity scale. This study will utilize the CTC version 3.0 for toxicity and adverse event reporting. A copy of the CTC version 3.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov). Any DLT will be reviewed by an Independent Safety Monitoring Committee (ISMC) who will confirm the grade and the causality Hematologic DLT: Any of the following will be considered DLT: • Any grade 3 or 4 hematologic toxicity, with the following exceptions: - Grade 3 or 4 AE which relationship with CYT107 administration is regarded as unlikely by the independent safety monitoring committee - Grade 3 AE (except neutropenia and lymphopenia mentioned just below) which abates and reaches a maximum of grade 2 in less than 7 days after a decrease of pegylated interfero | — |
Countries
France
Outcome results
None listed