Thymosin Alpha-1 in Combination With Peg-Interferon Alfa- 2a and Ribavirin for the Therapy of Chronic Hepatitis C Nonresponsive to the Combination of IFN and Ribavirin.

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Multicentre, Double Blinded Study In Patients With Chronic Hepatitis C Who Are Non-Responders To Prior Peginterferon Alpha + Ribavirin Therapy Comparing Treatment With Thymosin Alpha 1 + Peginterferon Alpha-2a Plus Ribavirin With Peginterferon Alpha-2a + Ribavirin + Placebo

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Biological: Thymosin alpha 1
* Drug: Ribavirin
* Biological: PEGinterferon alfa2a
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Age 18 Presence of HCV RNA measured by quantitative PCR 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) 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 Wash-out period of at least 6 months from previous therapy with PEGinterferon alpha plus ribavirin Negative pregnancy test prior (no more than 24 hours) to first study medication dose Exclusion Criteria: Use of systemic corticosteroids within 6 months of entry More than one previous course of therapy with PEGinterferon alpha plus ribavirin Any other liver disease Decompensated liver disease based on a history of hepatic encephalopathy, bleeding oesophageal varices, or ascites Decompensate or advanced liver cirrhosis (ChildPugh B or C) HIV infection diagnosed by HIV seropositivity and confirmed by Western blot Insulin-dependent Diabetes Mellitus Severe haemoglobinopathy Positive liver and kidney microsomal auto antibodies Positive anti thyroid antibodies Pregnancy as documented by a urine pregnancy test Alcohol or intravenous drug abuse within the previous 1 year 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 Any indication that the patient would not comply with the conditions of the study protocol Previous treatment with thymosin alpha 1 Patients with known hypersensitivity to any PEGinterferon and or ribavirin Patients with a history of severe depression that required either hospitalization or electroshock therapy or depression associated with suicide attempt Simultaneous participation in another investigational drug study or participation in any clinical trial involving investigational drugs within 3 months before study entry Presence of serious pulmonary or cardiovascular disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thymosin alpha 1<br>Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). | Biological: Thymosin alpha 1<br>* Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.<br>* Other names: Zadaxin;Drug: Ribavirin<br>* Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks<br>* Other names: Copegus;Biological: PEGinterferon alfa2a<br>* 180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks<br>* Other names: Pegasys;|
| Placebo Comparator: Placebo<br>Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). | Drug: Ribavirin<br>* Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks<br>* Other names: Copegus;Biological: PEGinterferon alfa2a<br>* 180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks<br>* Other names: Pegasys;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR) | The proportion of patients who were HCV RNA negative at the end of observation period. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Biochemical Response (SBR) | The proportion of patients with normal serum ALT at the end of observation period. | Week 72 | 
| End of Treatment Biochemical Response (EBR) | The proportion of patients with normal serum ALT at the end of treatment period. | Week 48 | 
| End of Treatment Virological Response [EVR] | The proportion of patients who were HCV RNA negative at the end of treatment period. | Week 48 | 
| Safety | Safety and tolerability were evaluated by AEs recording, laboratory (hematology and chemistry), ECG, and vital signs evaluations. All laboratory tests were centralized. | During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks) |