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

Condition	Treatment or Intervention	Phase
Hepatitis C Hepatitis C, Chronic	Drug: thymalfasin (thymosin alpha 1)  Drug: PEGinterferon alfa-2a	Phase III

Further Study Details: 

Expected Total Enrollment:  500

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Alabama
      University of Alabama - Knollwood Physician's Group, Mobile,  Alabama,  United States
Arizona
      Mayo Clinic, Scottsdale,  Arizona,  United States
California
      Scripps Clinic, La Jolla,  California,  United States
      Loma Linda University Medical Center, Loma Linda,  California,  United States
      Huntington Memorial Hospital, Pasadena,  California,  United States
      Gastroenterology Associates of East Bay Medical Group, Berkeley,  California,  United States
      San Mateo Medical Center, San Mateo,  California,  United States
      Kaiser Permanente, Sacramento,  California,  United States
      Kaiser Permanente, Santa Clara,  California,  United States
      University of California, Davis Medical Center, Sacramento,  California,  United States
      Advanced Clinical Research Institute, Anaheim,  California,  United States
      California Pacific Medical Center, San Francisco,  California,  United States
Colorado
      Arapahoe Gastroenterology, Littleton,  Colorado,  United States
District of Columbia
      Walter Reed Army Medical Center, Washington,  District of Columbia,  United States
      Washington Hospital Center, Washington,  District of Columbia,  United States
Florida
      University Of Miami Center for Liver Diseases, Miami,  Florida,  United States
      University of Florida, Gainesville,  Florida,  United States
      Mayo Clinic, Jacksonville,  Florida,  United States
Georgia
      Center for Digestive and Liver Health, Savannah,  Georgia,  United States
      Digestive Healthcare of Georgia, Atlanta,  Georgia,  United States
Idaho
      Idaho Gastroenterology Associates, Meridian,  Idaho,  United States
Illinois
      University of Chicago Hospital & Clinic, Chicago,  Illinois,  United States
Kentucky
      University of Louisville, Louisville,  Kentucky,  United States
Louisiana
      LSU Healthcare Network, New Orleans,  Louisiana,  United States
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  United States
      Chevy Chase Clinical Research, Chevy Chase,  Maryland,  United States
      Endoscopic Microsurgery Associates, Towson,  Maryland,  United States
Massachusetts
      New England Medical Center, Boston,  Massachusetts,  United States
Michigan
      William Beaumont Hospital, Royal Oak,  Michigan,  United States
Mississippi
      Mississippi Gastrointestinal Associates, Jackson,  Mississippi,  United States
Missouri
      VAMC, Kansas City,  Missouri,  United States
      Bradley Freilich MD, LLC, Kansas City,  Missouri,  United States
New York
      North Shore University Hospital, Manhasset,  New York,  United States
      VA Harbor HealthCare System, New York,  New York,  United States
      NYU Gastroenterology & Hepatology, New York,  New York,  United States
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  United States
      Carolinas Center for Liver Disease, Charlotte,  North Carolina,  United States
Ohio
      University of Cincinnati College of Medicine, Cincinnati,  Ohio,  United States
      Metro Health Medical Ctr., Cleveland,  Ohio,  United States
      The Cleveland Clinic Foundation, Cleveland,  Ohio,  United States
Oregon
      Oregon Health Sciences University, Portland,  Oregon,  United States
Pennsylvania
      Albert Einstein Medical Center, Philadelphia,  Pennsylvania,  United States
      University of Pennsylvania, Philadelphia,  Pennsylvania,  United States
      Jefferson University Physicians, Philadelphia,  Pennsylvania,  United States
Rhode Island
      Advanced Clinical Research, Providence,  Rhode Island,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  United States
Tennessee
      University of Tennessee Gastroenterology, Memphis,  Tennessee,  United States
Texas
      Baylor University Medical Ctr., Dallas,  Texas,  United States
      Baylor College of Medicine, Houston,  Texas,  United States
      Baylor, VAMC, Houston,  Texas,  United States
      Austin Gastroenterology PA, Austin,  Texas,  United States
Virginia
      Metropolitan Research, Fairfax,  Virginia,  United States
      McGuire DVAMC, Richmond,  Virginia,  United States
Wisconsin
      Wisconsin Center for Advanced Research, Milwaukee,  Wisconsin,  United States
Puerto Rico
      Fundacion de Investigacion de Diego, Santurce,  Puerto Rico
      Ponce School of Medicine, Ponce,  Puerto Rico

Study ID Numbers:  Ta1-CHC-2K0804
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  June 17, 2002
ClinicalTrials.gov Identifier:  NCT00039962
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08