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Protocol Details

Treatment of Chronic Delta Hepatitis with Lonafarnib

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-dk-0046

Sponsoring Institute

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Hepatitis;
Delta;
Treatment;
Lonafarnib

Recruitment Keyword(s)

Hepatitis D

Condition(s)

Hepatitis D

Investigational Drug(s)

Lonafarnib

Investigational Device(s)

None

Intervention(s)

Drug: Lonafarnib

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

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.

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Eligibility

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.


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Citations:

Glenn JS, Marsters JC Jr, Greenberg HB. Use of a prenylation inhibitor as a novel antiviral agent. J Virol. 1998 Nov;72(11):9303-6.

Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990 Mar;8 Suppl:S10-4; discussion S21-3.

Rosina F, Rizzetto M. Treatment of chronic type D (delta) hepatitis with alpha interferon. Semin Liver Dis. 1989 Nov;9(4):264-6.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Theo Heller, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10 RM 9C432B
10 CENTER DR
BETHESDA MD 20814
(301) 402-7147
theoh@intra.niddk.nih.gov

Vanessa Haynes-Williams, R.N.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Building 10
Room 6-5750
10 Center Drive
Bethesda, Maryland 20892
(301) 451-7007
vhaynes@mail.nih.gov

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT01495585

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