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.

Sigma-Tau Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Chronic Hepatitis C

Treatments: Biological: PEGinterferon alfa2a; Biological: Thymosin alpha 1; Drug: Ribavirin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01178996

ST1472-DM-03-004

2004-001277-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 552 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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552 participants in 2 patient groups, including a placebo group

Thymosin alpha 1

Experimental group

Description:

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).

Treatment:

Drug: Ribavirin

Biological: Thymosin alpha 1

Biological: PEGinterferon alfa2a

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Ribavirin

Drug: Placebo

Biological: PEGinterferon alfa2a