Pegylated Interferon to Treat Chronic Hepatitis D
This study will evaluate the safety and effectiveness of a long-acting form of alpha interferon called pegylated interferon in treating hepatitis D virus (HDV) infection. HDV only infects people who already have hepatitis B infection. HDV is often severe and progressive. Alpha interferon is the standard treatment for HDV, given by injection once a day or three times a week for up to 12 months. However, this treatment does not work for everyone, and those who respond usually relapse when the drug is stopped. The sustained-release form of the drug, pegylated interferon, is given just once a week. Pegylated interferon is more effective than standard interferon in hepatitis C patients, with patients experiencing longer-term improvement. This study will evaluate the effects of pegylated interferon on hepatitis D and hepatitis B. It will determine whether long-term therapy with this drug improves inflammation and scarring of the liver, thereby delaying or reversing cirrhosis, and whether the improvement can be maintained.
Patients with chronic hepatitis D over 6 years old may be eligible for this study. Participants will have a medical evaluation, including a history and physical examination, blood tests, routine urinalysis and 24-hour urine collection. Chest X-ray, electrocardiogram, abdominal ultrasound and liver biopsy will be done if these tests have not been done within the last year. In addition, depending on their age and individual health status, some patients may have exercise stress testing, an eye examination, hearing test, and psychiatric consultation. All patients will fill out a health-related quality of life questionnaire.
Patients will receive pegylated interferon by injection once a week and have blood tests to measure the effects of treatment on the liver and on HBV and HDV levels. The medical examination and liver biopsy will be repeated at the end of 12 months. Patients who improved with treatment may continue therapy long-term. Medical evaluations and liver biopsies will be repeated at 3 years and at 5 years.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Chronic Delta Hepatitis With Pegylated Interferon|
- Histological response at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Histological response at 5 years [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||August 2001|
|Estimated Study Completion Date:||October 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Drug: Peginterferon Alpha-2a
We propose to treat between 10 and 20 patients with chronic delta hepatitis with pegylated alpha interferon for up to five years. Patients with chronic delta hepatitis with raised serum aminotransferases, HBsAg and HDV RNA in serum, and moderate-to-severe chronic hepatitis on liver biopsy with HDV antigen will be enrolled. Patients will be monitored for at least three months with regular testing for ALT levels and will undergo admission for a thorough medical evaluation, portal pressure measurement and percutaneous liver biopsy before treatment. Pegylated interferon will then be started in a dose of 180 mcg weekly. At each clinic visit, patients will be questioned about side effects and symptoms and have blood taken for complete blood counts and routine liver tests (ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At 12-24 week intervals patients will undergo a physical examination and be tested for HBsAg, anti-HBs, HDV RNA, and prothrombin time. The dose of pegylated interferon will be adjusted based upon side effects and changes in ALT levels, aiming for optimal suppression of ALT elevations with acceptable tolerance. At 48 weeks (one year) and every 96 weeks (two years) thereafter, patients will be readmitted to the NIH Clinical Center for repeat thorough medical evaluation, portal pressure measurement and liver biopsy. The primary endpoint of therapy will be improvements in hepatic histology on liver biopsy done after 3 years of pegylated alpha interferon therapy. Several secondary endpoints will be measured, including changes in HDV RNA, loss of HBsAg, HDV staining in the liver biopsy, ALT levels, changes in portal pressures, quality of life, all at 1.3 and 5 years, and hepatic histology at 1 and 5 years. Patients will be maintained on pegylated interferon if it is adequately tolerated and there is an adequate "histological response," as defined by at least 3 point improvement in inflammatory score or 1 point improvement in fibrosis score of the HAI at each liver biopsy. Therapy will be stopped for: (1) intolerance to alpha interferon (which will be carefully defined), (2) lack of improvement in hepatic histology after 1, 3, or 5 years of therapy (histological nonresponse), or (3) a "complete response," i.e. loss of HDV RNA and HBsAg and development of anti-HBs.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Theo Heller, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|