Clinical Trial: Lonafarnib for Chronic Hepatitis D

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of Chronic Delta Hepatitis With Lonafarnib

Brief Summary:

Background:

• Chronic hepatitis D is a severe disease of the liver caused by infection with the hepatitis D virus. The hepatitis D virus can only infect a person who also has hepatitis B; therefore, people with delta hepatitis have both hepatitis B and hepatitis D virus infection. Most people with hepatitis D eventually develop cirrhosis, which causes scarring and damage to the liver. There is currently no effective treatment for chronic hepatitis D.
• Lonafarnib is a drug that was originally designed to treat different types of cancer. It may be able to prevent the hepatitis D virus from reproducing itself. However, it has not been tested on people with hepatitis D. Researchers want to study different doses of lonafarnib to see how they affect virus levels and other symptoms of hepatitis D.

Objectives:

- To test the safety and effectiveness of lonafarnib as a treatment for chronic hepatitis D.

Eligibility:

- Individuals at least 18 years of age who have chronic hepatitis D.

Design:

• Participants will be screened with a medical history and physical exam. They will have blood and urine tests, eye exams, and imaging studies of the liver and gall bladder. A liver biopsy may also be performed.
• Participants will receive either lonafarnib or placebo twice a day for 28 days. For the first 3 days, participants will stay in the hospital to have frequent blood tests. Participants will have four more clinic visits (on days 7, 14, 21, and 28) for blood and
  

  Detailed Summary: Chronic delta hepatitis is a serious form of chronic liver disease caused by infection with the hepatitis D virus (HDV), a small RNA virus that requires farnesylation of its major structural protein (HDV antigen) for replication. We propose to treat between 12 and 14 patients with chronic delta hepatitis using the farnesyltransferase inhibitor (FTI) lonafarnib for a duration of twenty-eight days. Farnesyltransferase inhibitors have not been used in the therapy of delta hepatitis. Patients with HBsAg and HDV RNA in serum, elevated aminotransferases, or moderate-to-severe chronic hepatitis and HDV antigen on liver biopsy will be enrolled. Before receiving therapy, patients will be monitored for at least three months with regular testing for alanine aminotransferase (ALT) levels and will undergo Clinical Center admission for medical evaluation and percutaneous liver biopsy. Two dosing groups of lonafarnib will be assessed, with a placebo cohort in each group. At each clinic visit, patients will be questioned about side effects and symptoms, undergo focused physical examination, and have blood drawn for complete blood counts, HDV RNA, and routine liver tests (including ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At two-week intervals, for a period of 28 days, patients will also be tested for HBsAg, anti-HBs, HBV DNA, and prothrombin time. At the end of 28 days of treatment, patients will undergo repeat physical examination, assessment of symptoms (using a symptom scale questionnaire), complete blood counts, routine liver tests, and hepatitis B and D viral markers. The primary therapeutic endpoint will be an improvement in quantitative serum HDV RNA levels after 28 days of lonafarnib therapy. The primary safety endpoint will be the ability to tolerate the drug at the prescribed dose for the 4 week duration. Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms. Therapy will be stopped for intolerance
  Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  

  Current Primary Outcome: Change in Quantitative Serum HDV RNA Levels After 28 Days of Lonafarnib Therapy. [ Time Frame: 28 days ]
  
  

  Original Primary Outcome: The primary endpoint of therapy will be an improvement in quantitative serum HDV RNA levels after 28 days of lonafarnib therapy.
  
  

  Current Secondary Outcome: ALT Levels [ Time Frame: 7 months ]
  
  

  Original Secondary Outcome: Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms.
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: December 16, 2011
  Date Started: December 2011
  Date Completion:
  Last Updated: July 18, 2016
  Last Verified: July 2016