Thymosin Plus PEG-Interferon in Hepatitis C Patients With Cirrhosis 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 with early cirrhosis or progression to 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)
* Drug: 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 3 months (12 weeks). Washout period of at least 6 months from previous therapy with IFN alone or IFN plus Ribavirin. Liver biopsy consistent with cirrhosis or progression to cirrhosis (METAVIR fibrosis score 3 to 4) due to chronic hepatitis C within the last 12 months before treatment starts, and at least 6 months after the end of the prior failed therapy. Cirrhosis classified as Child-Pugh A (no more than 6 points). Compensated liver disease with prothrombin time prolonged less than 3 seconds over control, total bilirubin < 2 mg/dl, and no history of hepatic encephalopathy, bleeding varices or a history of detection of stigmata of recent bleeding on existing varices or ascites. Ultrasound, CT scan, or MRI of the liver within 3 months of entry negative for HCC. Hematocrit > 30%, platelet count > 75,000, WBC > 2,500, and absolute neutrophil cell count > 1,500. 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. Evidence of drug-induced liver injury. Current use of any drug known to have or suspected of having therapeutic activity in hepatitis C, or any immunosuppressive drug (including corticosteroids). Evidence of any other liver disease including hepatitis B, hepatitis delta, alcoholic liver disease, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, alpha 1-antitrypsin deficiency, or Wilson's disease. Alpha-fetoprotein > 200 ng/mL. Child-Pugh B or C cirrhosis (score of 7 or more points), either currently or at any occasion in the past. Decompensated liver disease based on a history of hepatic encephalopathy, bleeding varices or a history of detection of stigmata of recent bleeding on existing 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. 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. Recipients of transplants. Patients with uncontrolled seizure disorder. 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 IFN a. Simultaneous participation in another investigational drug study, or participation in any clinical trial involving investigational drugs within 3 months of 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)|nan|
|Drug: 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, cirrhosis, liver