Chronic Hepatitis C
Conditions
Brief summary
The purpose of the study was to determine safety and efficacy of 48 weeks treatment with Thymosin alpha 1 (Talpha1) in combination with pegylated interferon (PEGIFN) alpha2a and ribavirin (RBV) in adult patients with chronic hepatitis C (CHC) already treated with, and not responding to previous courses of PEGIFN alpha plus RBV combination therapy, in comparison with a concurrent group treated with PEG IFN alpha2a in combination with RBV and placebo.
Interventions
BIOLOGICALThymosin alpha 1
Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.
DRUGRibavirin
Ribavirin 1000 mg (\<75 kg) or 1200 mg (\>75 kg) daily with food divided in two doses orally for 48 weeks
BIOLOGICALPEGinterferon alfa2a
180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks
DRUGPlacebo
Placebo
Sponsors
SciClone Pharmaceuticals
sigma-tau i.f.r. S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. Age 18 3. Presence of HCV RNA measured by quantitative PCR 4. Non responder to previous approved doses of therapy with PEGinterferon alpha plus ribavirin. Patients must have been treated for at least 12 weeks with documented HCV RNA quantitative not showing major of 2 log10 HCV RNA reduction or patients treated for at least 24 weeks with documented HCV RNA qualitative not showing a virological response (viral RNA clearance) 5. Liver biopsy consistent with a diagnosis of chronic hepatitis C or histological cirrhosis. Biopsy will not be required if the patient can produce a biopsy performed within the year preceding the randomization day and was performed at least 6 months after the end of the latter course of therapy 6. Wash-out period of at least 6 months from previous therapy with PEGinterferon alpha plus ribavirin 7. Negative pregnancy test prior (no more than 24 hours) to first study medication dose
Exclusion criteria
1. Use of systemic corticosteroids within 6 months of entry 2. More than one previous course of therapy with PEGinterferon alpha plus ribavirin 3. Any other liver disease 4. Decompensated liver disease based on a history of hepatic encephalopathy, bleeding oesophageal varices, or ascites 5. Decompensate or advanced liver cirrhosis (ChildPugh B or C) 6. HIV infection diagnosed by HIV seropositivity and confirmed by Western blot 7. Insulin-dependent Diabetes Mellitus 8. Severe haemoglobinopathy 9. Positive liver and kidney microsomal auto antibodies 10. Positive anti thyroid antibodies 11. Pregnancy as documented by a urine pregnancy test 12. Alcohol or intravenous drug abuse within the previous 1 year 13. Patients who are in poor medical or psychiatric conditions, or who have any non-malignant systemic disease that, in the opinion of the Investigator, would make it unlikely that the patient could complete the study protocol 14. Any indication that the patient would not comply with the conditions of the study protocol 15. Previous treatment with thymosin alpha 1 16. Patients with known hypersensitivity to any PEGinterferon and or ribavirin 17. Patients with a history of severe depression that required either hospitalization or electroshock therapy or depression associated with suicide attempt 18. Simultaneous participation in another investigational drug study or participation in any clinical trial involving investigational drugs within 3 months before study entry 19. Presence of serious pulmonary or cardiovascular disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR) | Week 72 | The proportion of patients who were HCV RNA negative at the end of observation period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Biochemical Response (SBR) | Week 72 | The proportion of patients with normal serum ALT at the end of observation period. |
| End of Treatment Biochemical Response (EBR) | Week 48 | The proportion of patients with normal serum ALT at the end of treatment period. |
| End of Treatment Virological Response [EVR] | Week 48 | The proportion of patients who were HCV RNA negative at the end of treatment period. |
| Safety | During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks) | Safety and tolerability were evaluated by AEs recording, laboratory (hematology and chemistry), ECG, and vital signs evaluations. All laboratory tests were centralized. |
Countries
France, Germany, Greece, Italy, Spain
Outcome results
None listed