Lonafarnib for Chronic Hepatitis D

NCT01495585 | Completed Phase 2 Results

• 2 other identifiers: 12004612-DK-0046
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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 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....

Conditions

Hepatitis D

Keywords

Hepatitis; Delta; Treatment; Lonafarnib; Hepatitis D

Outcome Measures

Primary Outcomes (1)

• Change in Quantitative Serum HDV RNA Levels After 28 Days of Lonafarnib Therapy.

  28 days

Secondary Outcomes (1)

• ALT Levels

  7 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo control

Other: Placebo

Group 1

EXPERIMENTAL

lonafarnib 100mg

Drug: Lonafarnib

Group 2

EXPERIMENTAL

lonafarnib 200mg

Drug: Lonafarnib

Interventions

Lonafarnib DRUG

Commercially approved products used to test the research hypothesis

Group 1; Group 2

Placebo OTHER

Placebo control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or above, male or female.
• 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.
• Presence of anti-HDV in serum.
• 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).
• Presence of HDV antigen in liver tissue or HDV RNA in serum.
• Written informed consent.

You may not qualify if:

• 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.
• 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.
• Systemic immunosuppressive therapy within the previous 2 months.
• 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).
• Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year.
• Evidence of hepatocellular carcinoma.
• Evidence of concurrent hepatitis C infection with positive serum HCV RNA.
• Any experimental therapy apart from pegylated interferon within 6 months prior to enrollment.
• Diagnosis of malignancy in the five years prior to the enrollment with exception granted to superficial dermatologic malignancies.
• Evidence of HIV co-infection; HIV (Omega) antibody positivity on serum testing.
• Concurrent usage of statins as these drugs inhibit mevalonate synthesis which reduces protein prenylation.
• Concurrent usage of moderate and strong CYP3A inhibitors and inducers.
• Inability to understand or sign informed consent.
• Any other condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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. doi: 10.1128/JVI.72.11.9303-9306.1998.

  PMID: 9765479 BACKGROUND

• Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990 Mar;8 Suppl:S10-4; discussion S21-3. doi: 10.1016/0264-410x(90)90207-3.

  PMID: 2183511 BACKGROUND

• Rosina F, Rizzetto M. Treatment of chronic type D (delta) hepatitis with alpha interferon. Semin Liver Dis. 1989 Nov;9(4):264-6. doi: 10.1055/s-2008-1040521. No abstract available.

  PMID: 2690350 BACKGROUND

• Kefalakes H, Koh C, Sidney J, Amanakis G, Sette A, Heller T, Rehermann B. Hepatitis D Virus-Specific CD8+ T Cells Have a Memory-Like Phenotype Associated With Viral Immune Escape in Patients With Chronic Hepatitis D Virus Infection. Gastroenterology. 2019 May;156(6):1805-1819.e9. doi: 10.1053/j.gastro.2019.01.035. Epub 2019 Jan 18.

  PMID: 30664876 DERIVED

• Koh C, Canini L, Dahari H, Zhao X, Uprichard SL, Haynes-Williams V, Winters MA, Subramanya G, Cooper SL, Pinto P, Wolff EF, Bishop R, Ai Thanda Han M, Cotler SJ, Kleiner DE, Keskin O, Idilman R, Yurdaydin C, Glenn JS, Heller T. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015 Oct;15(10):1167-1174. doi: 10.1016/S1473-3099(15)00074-2. Epub 2015 Jul 16.

  PMID: 26189433 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis D; Hepatitis

Interventions

lonafarnib

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Dr. Theo Heller
• Organization: National Insitute of DIabetes and Digestive and Kidney Diseases

hellert@mail.nih.gov

301-402-7147

Study Officials

• Theo Heller, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 20, 2011
• Study Start: December 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 31, 2016
• Results First Posted: August 31, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)