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.

Chronic Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01178996
• Other study ID #: ST1472-DM-03-004
• Secondary ID: 2004-001277-25
• Status: Completed
• Phase: Phase 3
• First received: August 9, 2010
• Last updated: August 9, 2010
• Start date: December 2004
• Est. completion date: July 2009

Study information

• Verified date: August 2010
• Source: sigma-tau i.f.r. S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. completion date: July 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Biological:
• Thymosin alpha 1
Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.

Drug:
• Ribavirin
Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks

Biological:
• PEGinterferon alfa2a
180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks

Drug:
• Placebo
Placebo

Locations

Country	Name	City	State
France	Hôpital Necker	Paris
Germany	Universitätsklinikum Tübingen	Tübingen
Greece	University Hospital of Ioannina	Ioannina
Italy	Policlinico S.Orsola-Malpighi	Bologna
Italy	Ospedale Cardarelli	Napoli
Italy	Università Cattolica del Sacro Cuore	Rome
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista	Turin
Spain	Hospital del Mar	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
sigma-tau i.f.r. S.p.A.	SciClone Pharmaceuticals

Countries where clinical trial is conducted

France,  Germany,  Greece,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Virological Response (SVR)	The proportion of patients who were HCV RNA negative at the end of observation period.	Week 72	No
Secondary	Sustained Biochemical Response (SBR)	The proportion of patients with normal serum ALT at the end of observation period.	Week 72	No
Secondary	End of Treatment Biochemical Response (EBR)	The proportion of patients with normal serum ALT at the end of treatment period.	Week 48	No
Secondary	End of Treatment Virological Response [EVR]	The proportion of patients who were HCV RNA negative at the end of treatment period.	Week 48	No
Secondary	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)	Yes