Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir
2 other identifiers
interventional
22
1 country
1
Brief Summary
Background: \- Chronic hepatitis D is a liver disease caused by the hepatitis D virus (HDV). It can be severe and progressive. Most people with hepatitis D will develop scarring and damage to the liver. There is no FDA approved drug to treat chronic hepatitis D. Researchers want to know if the drugs lonafarnib and ritonavir can help people with chronic hepatitis D. Objective: \- To find out if treatment of hepatitis D with lonafarnib and ritonavir is safe and effective. Eligibility: \- People 18 years of age and older with chronic hepatitis D. They must not have HIV or other major illnesses. Design:
- Participants will be screened with medical history, physical exams, and blood tests.
- Participants will have 24 weeks of treatment. They will then have 24 weeks of follow-up.
- Participants will be in 1 of 6 treatment groups. Those in each group will receive different doses of the study drugs. Some groups will start with placebo but will receive treatment after 3 months of placebo.
- Participants will also take drugs to treat hepatitis B.
- Participants will have many visits. These will include:
- One three-day stay at the Clinical Center
- Physical exams
- EKG: small sticky patches will be put on the chest, arms, and legs to trace heart rhythm
- Ultrasounds of the abdomen
- Urine and blood tests
- Stool samples
- Eye exams
- Evaluations by a reproductive endocrinologist (women) or urologist (men). Men may provide a sperm sample (optional).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2015
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 29, 2015
CompletedStudy Start
First participant enrolled
July 29, 2015
CompletedFirst Posted
Study publicly available on registry
July 30, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 23, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 23, 2017
CompletedResults Posted
Study results publicly available
May 24, 2018
CompletedSeptember 25, 2018
February 23, 2017
1.6 years
July 29, 2015
April 24, 2018
August 27, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Decline of Hepatitis Delta Virus (HDV) RNA Quantitative Measurements of >2 Logs From Baseline at 12 Weeks of Treatment
The number of participants who experienced a \> 2 log IU/mL decline in serum HDV RNA at 12 weeks of treatment
12 weeks
Number of Participants With Decline of HDV RNA Quantitative Measurement of > 2 Logs From Baseline at 24 Weeks of Treatment
The number of participants who experienced a \> 2 log IU/mL decline in serum HDV RNA levels at 24 weeks of treatment
24 weeks
Study Arms (6)
Group 1
EXPERIMENTALLonafarnib/Ritonavir at 50 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Group 2
EXPERIMENTALLonafarnib/Ritonavir at 75 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Group 3
EXPERIMENTALLonafarnib/Ritonavir at 100 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Group 4
EXPERIMENTALPlacebo for 12 weeks then Lonafarnib/Ritonavir at 50 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Group 5
EXPERIMENTALPlacebo for 12 weeks then Lonafarnib/Ritonavir at 75 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Group 6
EXPERIMENTALPlacebo for 12 weeks then Lonafarnib/Ritonavir at 100 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Interventions
prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
FDA approved drug for use of boosting other drugs. Will be used to boost Lonafarnib as they both use the same cytochrome P450 system. Will be administered at 100 mg daily.
Eligibility Criteria
You may qualify if:
- Age 18 years or above, male or female.
- Serum alanine or aspartate aminotransferase (ALT or AST) activities above the upper limit of normal (ALT greater than or equal to 20 or AST greater than or equal to 20 U/L in females and ALT greater than or equal to 30 or AST greater than or equal to 30 U/L in males) on an average of three determinations taken during the previous 6 months at the NIH clinical center. The mean of the three determinations will be defined as baseline levels.
- Presence of anti-HDV in serum.
- Presence of quantifiable HDV RNA in serum.
You may not qualify if:
- Pregnancy, active breast-feeding, 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. In total, the participant and their partner must utilize two forms of contraception and one method must include a barrier method.
- 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 hepatitis c virus (HCV) RNA.
- Any experimental therapy or pegylated interferon therapy 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 1/2 viral RNA or antigen on serum testing.
- Concurrent usage of statins as these drugs inhibits mevalonate synthesis, which reduces protein prenylation.
- Concurrent usage of moderate and strong cytochrome p450, family 3, subfamily A (CYP3A) inhibitors and inducers.
- Use of any prescription, nonprescription or natural medicine (herbal) medications unless the use of medication is medically necessary with appropriate monitoring.
- Concurrent usage of alpha 1 adrenoreceptor antagonist, antiarrhythmic, pimozide, sildenafil, sedative and hypnotics, ergot and St. John s Wort due to possible effect of ritonavir on hepatic metabolism of these drugs resulting in potentially life threatening side effects.
- Clinically significant baseline EKG abnormalities.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (1)
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: 30664876DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Christopher Koh, MD
- Organization
- NIDDK
Study Officials
- PRINCIPAL INVESTIGATOR
Theo Heller, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 29, 2015
First Posted
July 30, 2015
Study Start
July 29, 2015
Primary Completion
February 23, 2017
Study Completion
February 23, 2017
Last Updated
September 25, 2018
Results First Posted
May 24, 2018
Record last verified: 2017-02-23