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 Alfa-2a + Ribavirin With Peginterferon Alfa-2a + Ribavirin + Placebo. - N/A

• Conditions: treatment of patients with Chronic Hepatitis C who are Non-responders to a course with approved doses of PEGinterferon alpha + Ribavirin

• Registration Number: EUCTR2004-001277-25-DE
• Lead Sponsor: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-09-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

1. Signed written informed consent.
2. Age > 18 or less than/equal to 70.
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 greater than/equal to 2 log ^10 HCV RNA reduction or patients treated for at least 24 weeks with documented HCV RNA qualitative not showing a virological response (i.e. viral RNA clearance).
5. Liver biopsy consistent with a diagnosis of chronic hepatitis C or histological cirrhosis. Biopsy will not be required if: The NON-CIRRHOTIC 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; THE CIRRHOTIC PATIENT CAN PRODUCE A BIOPSY PERFORMED WITHIN THIRTY MONTHS PRECEDING THE RANDOMIZATION DAY.
6. Wash-out period of at least 6 months from previous therapy with PEGinterferon alpha plus ribavirin.
7. Compensated liver disease (if cirrhotic, Child-Pugh A only) with prothrombin time prolonged less than 0.3 INR (INR normal range between 0,9 and 1,25) over control, serum albumin stable and within normal limits, total bilirubin less than/equal to 2 mg/dl, and no history of hepatic encephalopathy, bleeding oesophageal varices or ascites.
8. An ultrasound of the liver within 3 months of entry negative for HCC.
9. Haematocrit greater than/equal to 30%, platelet count greater than/equal to 75 x 10^3/mm^3, WBC greater than/equal to 2.5 x 10^3/mm^3, total neutrophil granulocytes count greater than/equal to 1.5 x 10^3/mm^3, and haemoglobin greater than/equal to 12 g/dl for women and greater than/equal to 13 g/dl for men.
10. Adequate renal function as demonstrated by serum creatinine level within the normal range.
11. Normal TSH or evidence of proper thyroid hormone replacement.
12. All women of childbearing potential, either participating in the study as a patient or partners of male patients participating in the study, must agree to practice abstinence from sexual intercourses or to use two reliable forms of effective contraception (combined) during the treatment period and follow-up. These may include, but are not limited to, birth control pills, IUDs, condoms, diaphragms, implants, surgical sterilization. Because ribavirin may be transmitted in semen, it is recommended that one method of contraception be a barrier type.
13. Negative pregnancy test prior (no more than 24 hours) to first study medication dose.

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

1. Use of systemic corticosteroids within 6 months of entry.
2. Use of any drug known to be hepatotoxic, any drug (other than the study drugs) known to have or suspected of having therapeutic activity in hepatitis C, or of any immunosupressive drug (including corticosteroids).
3. a-fetoprotein > 200 ng/mL.
4. Any other liver disease including hepatitis B, hepatitis delta, alcoholic liver disease, drug-induced liver injury, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, haemochromatosis, alpha 1-antitrypsin deficiency, or Wilson’s disease. (Except for hepatitis B and haemochromatosis, clinical judgment should be adequate to rule out the co-existence of other liver diseases and laboratory testing should ordinarily not be required.)
5. Decompensated liver disease based on a history of hepatic encephalopathy, bleeding oesophageal varices, or ascites.
6. Decompensate or advanced liver cirrhosis (Child-Pugh B or C).
7. Stage of oesophageal varices grade F2 or more (evaluated by endoscopy exam).
8. HIV infection diagnosed by HIV seropositivity and confirmed by Western blot.
9. Concomitant or prior history of malignancy other than surgically cured in situ carcinoma of the cervix.
10. Active infectious process other than HCV that is not of a self-limiting nature. TB and AIDS are examples of infectious processes that are not of a self-limiting nature.
11. Serum ANA >1:320; rheumatoid arthritis or other clinical indications of autoimmune disease.
12. Insulin-dependent Diabetes Mellitus.
13. Clinical evidence of retinopathy.
14. Severe haemoglobinopathy.
15. Positive liver and kidney microsomal auto antibodies.
16. Positive anti-thyroid antibodies.
17. Lactation; Pregnancy as documented by a urine pregnancy test. The patient and female partners of male patients must agree to practice an adequate method of birth control (as well described in the inclusion criteria) for the duration of the study, including the follow-up period.
18. Alcohol or intravenous drug abuse within the previous 1 year.
19. 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.
20. Any indication that the patient would not comply with the conditions of the study protocol.
21. Previous treatment with thymosin alpha 1.
22. Patients with known hypersensitivity to any PEGinterferon and/or ribavirin.
23. Patients with a history of severe depression that required either hospitalization or electroshock therapy; or depression associated with suicide attempt.
24. Simultaneous participation in another investigational drug study or participation in any clinical trial involving investigational drugs within 3 months before study entry.
25. Presence of serious pulmonary or cardiovascular disorders.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified