Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Lonafarnib for Chronic Hepatitis D

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01495585
Recruitment Status : Completed
First Posted : December 20, 2011
Results First Posted : August 31, 2016
Last Update Posted : August 31, 2016
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Tracking Information
First Submitted Date  ICMJE December 16, 2011
First Posted Date  ICMJE December 20, 2011
Results First Submitted Date  ICMJE April 28, 2016
Results First Posted Date  ICMJE August 31, 2016
Last Update Posted Date August 31, 2016
Study Start Date  ICMJE December 2011
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
Change in Quantitative Serum HDV RNA Levels After 28 Days of Lonafarnib Therapy. [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2011)
The primary endpoint of therapy will be an improvement in quantitative serum HDV RNA levels after 28 days of lonafarnib therapy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
ALT Levels [ Time Frame: 7 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2011)
Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lonafarnib for Chronic Hepatitis D
Official Title  ICMJE 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 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....
Detailed Description 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 to lonafarnib (which will be carefully defined). This study is designed as a phase 2a study assessing the safety, tolerance and antiviral activity of two dose levels of lonafarnib, a farnesyltransferase inhibitor.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis D
Intervention  ICMJE
  • Drug: Lonafarnib
    Commercially approved products used to test the research hypothesis
  • Other: Placebo
    Placebo control
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo control
    Intervention: Other: Placebo
  • Experimental: Group 1
    lonafarnib 100mg
    Intervention: Drug: Lonafarnib
  • Experimental: Group 2
    lonafarnib 200mg
    Intervention: Drug: Lonafarnib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 16, 2011)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01495585
Other Study ID Numbers  ICMJE 120046
12-DK-0046 ( Other Identifier: NIH Clinical Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified data with outside collaborators
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Theo Heller, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP