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

Hepatitis C Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00040027
• Other study ID #: Ta1-CHC-2K0803a
• Status: Completed
• Phase: Phase 3
• First received: June 18, 2002
• Last updated: January 8, 2008
• Start date: April 2002

Study information

• Verified date: January 2008
• Source: SciClone Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• thymalfasin (thymosin alpha 1) + PEGinterferon alfa-2a

• placebo + PEGinterferon alfa-2a

Locations

Country	Name	City	State
Puerto Rico	Ponce School of Medicine	Ponce
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Gastroenterology Associates of East Bay Medical Group	Berkeley	California
United States	New England Medical Center	Boston	Massachusetts
United States	Carolinas Center for Liver Diseases	Charlotte	North Carolina
United States	Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	University of Chicago Hospital & Clinic	Chicago	Illinois
United States	University of Cincinnati - College of Medicine	Cincinnati	Ohio
United States	Metro Health Medical Center, GI Division	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Metropolitan Research	Fairfax	Virginia
United States	University of Florida	Gainesville	Florida
United States	Baylor, VAMC	Houston	Texas
United States	Mississippi Gastrointestinal Associates	Jackson	Mississippi
United States	Mayo Clinic	Jacksonville	Florida
United States	VAMC	Kansas City	Missouri
United States	Scripps Clinic	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Hepatitis C Treatment Centers, Inc.	Louisville	Kentucky
United States	Liver Research Center - University of Louisville	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	GI Center MidSouth	Memphis	Tennessee
United States	University of Tennessee Gastroenterology	Memphis	Tennessee
United States	Idaho Gastroenterology Associates	Meridian	Idaho
United States	University of Miami Center for Liver Diseases	Miami	Florida
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	University of Alabama - Knollwood Physician's Group Bldg.	Mobile	Alabama
United States	Louisiana State University Healthcare Network	New Orleans	Louisiana
United States	Bronx VA Medical Center	New York	New York
United States	NY VAMC	New York	New York
United States	NYU Hospitals Center	New York	New York
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	McGuire Research Institute	Richmond	Virginia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Saint Louis University Hospital	SainT Louis	Missouri
United States	California Pacific Medical Center	San Francisco	California
United States	Veterans Administration Medical Center GI Section (111B)	San Francisco	California
United States	Center for Digestive and Liver Health	Savannah	Georgia
United States	Mayo Clinic	Scottsdale	Arizona
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
SciClone Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico,