Thymosin Plus PEG-Interferon in Non-Cirrhotic Hepatitis C Patients Who Did Not Respond to Interferon or Interferon Plus Ribavirin

Study Overview
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Brief Summary
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Chronic hepatitis C infection is one of the leading causes of chronic liver disease in the United States. Approximately one-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection in previously untreated patients is successful in only about half of patients. There is no established therapy for non-responders. This is a randomized, double-blinded, multicenter trial to determine the effectiveness of thymosin alpha 1 (thymalfasin) 1.6 mg twice weekly plus PEGinterferon alfa-2a 180 ug/wk compared to placebo plus PEGinterferon alfa-2a in adults with chronic hepatitis C without cirrhosis who are non-responders to previous treatment with interferon or interferon plus ribavirin. The definition of non-response requires a positive HCV RNA test at the end of a course of at least 12 weeks of therapy. Patients will receive treatment for 12 months, and will be followed-up for a further 6 months after the end of therapy.

Conditions
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Hepatitis C, Hepatitis C, Chronic

Intervention / Treatment
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* Drug: thymalfasin (thymosin alpha 1) + PEGinterferon alfa-2a
* Drug: placebo + PEGinterferon alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed written informed consent. Age over 18 years old. Presence of HCV RNA measured by qualitative PCR. Nonresponder to a previous course of therapy with either IFN alone or IFN plus ribavirin. The patient must have been treated for at least 12 weeks. Washout period of at least 6 months from previous therapy with IFN alone or IFN plus Ribavirin. Liver biopsy consistent with chronic hepatitis C within the last 12 months before treatment starts, and at least 6 months after the end of the prior failed therapy. No clinical or histological evidence of cirrhosis (METAVIR fibrosis score 0 to 3). Compensated liver disease with prothrombin time prolonged less than 3 seconds over control, serum albumin stable and within normal limits, total bilirubin < 2 mg/dl, and no history of hepatic encephalopathy, esophageal varices or ascites. Ultrasound, CT scan, or MRI of the liver within 3 months of entry negative for HCC. Hematocrit > 30%, platelet count > 100 x 109/L, WBC > 3 x 109/L, and polymorphonuclear white cell count > 1.5 x 109/L. Adequate renal function as demonstrated by serum creatinine level < 2.0 mg/dL. Normal TSH or adequately controlled thyroid function. If the patient is a woman, she is using a definitive method of birth control in consultation with her physician, or is surgically sterile or post-menopausal. Exclusion criteria: Use of systemic corticosteroids within 6 months of entry. Current 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 immunosuppressive drug (including corticosteroids). Any other liver disease including hepatitis B, hepatitis delta, alcoholic liver disease, drug-induced liver injury, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, alpha 1-antitrypsin deficiency, or Wilson's disease. Alpha-fetoprotein > 200 ng/mL. Current or past diagnosis of cirrhosis. Evidence of portal hypertension either by Doppler ultrasonography or gastrointestinal endoscopy. Decompensated liver disease based on a history of hepatic encephalopathy, esophageal varices, or ascites. HIV infection diagnosed by HIV seropositivity and confirmed by Western blot. Concomitant or prior history of malignancy other than curatively treated skin cancer or surgically cured in situ carcinoma of the cervix. Active infectious process other than HCV that is not of a self-limited nature (eg. TB or AIDS). Rheumatoid arthritis or other autoimmune disease (serum ANA > 1:160). Pregnancy as documented by a urine pregnancy test. Alcohol or intravenous drug abuse within the previous 1 year. Chronic use of methadone. Patients who are poor medical risk 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 protocol. Patients with a history of severe depression that required either hospitalization or electroshock therapy; or depression associated with suicide attempt. Patients with significant pre-existing cardiac or pulmonary disease. 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 IFNa. Simultaneous participation in another investigational drug study, or participation in any clinical trial involving investigational drugs with 3 months before study entry. Family history of intracerebral hemorrhage.

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: thymalfasin (thymosin alpha 1) + PEGinterferon alfa-2a|nan|
|Drug: placebo + PEGinterferon alfa-2a|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis C, hepatitis C, chronic