NCT01495585

Treatment of Chronic Delta Hepatitis With Lonafarnib

Completed Phase 2 Results posted Last updated 18 July 2016

What this trial tests

Phase 2 trial testing Lonafarnib in Hepatitis D in 14 participants. Completed in 1 April 2015.

Timeline

1 December 2011

Primary endpoint
1 April 2015

1 April 2015

Quick facts

Lead sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	14
Start date	1 December 2011
Primary completion	1 April 2015
Estimated completion	1 April 2015
Sites	1 location across United States

Drugs / interventions tested

• Lonafarnib (LONAFARNIB) — full drug profile →
• Placebo

Conditions studied

• Hepatitis D — all drugs for Hepatitis D →

Sponsor

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

Who can join

18 and older, any sex, with Hepatitis D. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change in Quantitative Serum HDV RNA Levels After 28 Days of Lonafarnib Therapy.
  Time frame: 28 days

Sponsor's own description

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....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial.
   Koh C, Canini L, Dahari H, Zhao X, et al · · 2015 · cited 197× · PMID 26189433 · DOI 10.1016/s1473-3099(15)00074-2
2. Lonafarnib: First Approval.
   Dhillon S. · · 2021 · cited 88× · PMID 33590450 · DOI 10.1007/s40265-020-01464-z
3. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery.
   Noureddin M, Gish R. · · 2014 · cited 70× · PMID 24293018 · DOI 10.1007/s11894-013-0365-x
4. Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.
   Yuan Y, Li P, Li J, Zhao Q, et al · · 2024 · cited 56× · PMID 38485938 · DOI 10.1038/s41392-024-01759-7
5. Hepatitis D Virus-Specific CD8<sup>+</sup> T Cells Have a Memory-Like Phenotype Associated With Viral Immune Escape in Patients With Chronic Hepatitis D Virus Infection.
   Kefalakes H, Koh C, Sidney J, Amanakis G, et al · · 2019 · cited 46× · PMID 30664876 · DOI 10.1053/j.gastro.2019.01.035
6. Pharmacokinetics and pharmacodynamics modeling of lonafarnib in patients with chronic hepatitis delta virus infection.
   Canini L, Koh C, Cotler SJ, Uprichard SL, et al · · 2017 · cited 10× · PMID 29404459 · DOI 10.1002/hep4.1043
7. Hepatitis Delta: Current Knowledge and Future Directions.
   Lange M, Zaret D, Kushner T. · · 2022 · cited 5× · PMID 36397990
8. Hepatitis D virus (HDV): investigational therapeutic agents in clinical trials.
   Asif B, Koh C. · · 2022 · cited 5× · PMID 34482769 · DOI 10.1080/13543784.2021.1977795