Lonafarnib for Chronic Hepatitis D
Condition: Hepatitis D
MeSH terms: Hepatitis A; Hepatitis D; Hepatitis
Intervention: Lonafarnib; Placebo
Intervention description: Commercially approved products used to test the research hypothesis; Placebo control
Intervention MeSH terms: Lonafarnib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis; Delta; Treatment; Lonafarnib; Hepatitis D

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
           urine tests. Eye exams and heart function tests will also be given. Men may be asked to
           provide sperm samples for further testing.

        -  After the 28 days of treatment, participants will stop taking the drug or placebo. They
           will have regular followup visits for up to 6 months after stopping treatment....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age 18 years or above, male or female.

               2. Serum alanine or aspartate aminotransferase activities above the upper limit of
                  normal (ALT > 41 or AST > 31 U/L) on an average of three determinations taken
                  during the previous 6 months. The mean of the three determinations will be
                  defined as baseline levels.

               3. Presence of anti-HDV in serum.

               4. Evidence of chronic hepatitis on liver biopsy done within the previous 12 months
                  with a necroinflammatory score in histology activity index of at least 5 (out of
                  a maximum of 18) and at least 1 for hepatic fibrosis (out of a maximum of 6).

               5. Presence of HDV antigen in liver tissue or HDV RNA in serum.

               6. Written informed consent.

        EXCLUSION CRITERIA:

          1. Decompensated liver disease, defined by bilirubin > 4mg/dL, albumin < 3.0 gm/dL,
             prothrombin time > 2 sec prolonged, or history of bleeding esophageal varices, ascites
             or hepatic encephalopathy. Laboratory abnormalities that are not thought to be due to
             liver disease may not necessarily require exclusion. Patients with ALT levels greater
             than 1000 U/L (> 25 times ULN) will not be enrolled but may be followed until three
             determinations are below this level.

          2. Pregnancy or inability to practice adequate contraception, in women of childbearing
             potential or in spouses of such women. Adequate contraception is defined as vasectomy
             in men, tubal ligation in women, or use of two barrier methods such as condoms and
             spermicide combination, birth control pills, an intrauterine device, Depo-Provera, or
             Norplant.

          3. Significant systemic or major illnesses other than liver disease, including, but not
             limited to, congestive heart failure, renal failure (eGFR < 50 ml/min), organ
             transplantation, serious psychiatric disease or depression (only if felt to be at high
             risk by the NIH psychiatric consultation service), and active coronary artery disease.

          4. Systemic immunosuppressive therapy within the previous 2 months.

          5. Evidence of another form of liver disease in addition to viral hepatitis (for example
             autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis,
             Wilson disease, alcoholic liver disease, nonalcoholic steatohepatitis (but not
             steatosis), hemochromatosis, or alpha-1-antitrypsin deficiency).

          6. Active substance abuse, such as alcohol, inhaled or injection drugs within the
             previous year.

          7. Evidence of hepatocellular carcinoma.

          8. Evidence of concurrent hepatitis C infection with positive serum HCV RNA.

          9. Any experimental therapy apart from pegylated interferon within 6 months prior to
             enrollment.

         10. Diagnosis of malignancy in the five years prior to the enrollment with exception
             granted to superficial dermatologic malignancies.

         11. Evidence of HIV co-infection; HIV (Omega) antibody positivity on serum testing.

         12. Concurrent usage of statins as these drugs inhibit mevalonate synthesis which reduces
             protein prenylation.

         13. Concurrent usage of moderate and strong CYP3A inhibitors and inducers.

         14. Inability to understand or sign informed consent.

         15. Any other condition, which in the opinion of the investigators would impede the
             patient s participation or compliance in the study.