Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon
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|ClinicalTrials.gov Identifier: NCT03600714|
Recruitment Status : Completed
First Posted : July 26, 2018
Results First Posted : December 1, 2021
Last Update Posted : December 14, 2021
Infection with hepatitis D virus leads to a chronic liver disease with no effective treatment. Lonafarnib has improved hepatitis D virus levels in blood, but the medication still needs more research. Ritonavir makes other drugs more effective and is used with lonafarnib to make it more effective. Lambda interferon stimulates the body s response to viruses. Researchers want to see if combining these drugs fights hepatitis D and helps the liver.
To see if combining lonafarnib, ritonavir, and lambda interferon is safe and effective to treat chronic hepatitis D infection.
Adults at least 18 years old with chronic hepatitis D infection
Participants will be screened with a physical exam, medical history, and blood and urine tests.
Throughout the study, all participants will:
- Follow rules for medicine, food, and contraception
- Take hepatitis B medicine
- Have weight checked
- Have routine blood and urine tests
- Give stool samples
- Female participants will have pregnancy tests.
Participants will have 3 visits before treatment. They will repeat screening tests and have a heart test and liver scan.
Participants will have a 5-day inpatient stay. They will:
- Baseline blood and urine tests
- Have eye tests
- Answer health questions
- Have a liver sample taken and liver blood pressure measured. Participants will be sedated.
- Have reproductive tests
- Start the study drugs and have blood draws
Over 24 weeks of treatment, participants will:
-Take 2 study drugs by mouth every day and 1 as a weekly injection
|Condition or disease||Intervention/treatment||Phase|
|Liver Disease Hepatitis D||Drug: Peg-interferon lambda Drug: Lonafarnib Drug: Ritonavir||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon|
|Actual Study Start Date :||August 1, 2018|
|Actual Primary Completion Date :||February 5, 2020|
|Actual Study Completion Date :||August 11, 2020|
Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Drug: Peg-interferon lambda
Peg-interferon Lambda is a covalent conjugate of human recombinant non- pegylated interferon (IFN) lambda and a 20-kDa linear pegylated (PEG) chain.
Oral prenylation inhibitor
Booster of lonafarnib action
- Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs [ Time Frame: Baseline and 24 weeks ]Decline of HDV RNA viral titer of >2 logs from baseline at 24 weeks of therapy
- Number of Participants Who Discontinue Medication [ Time Frame: 24 weeks ]Discontinuation of the medication before 24 weeks by the clinical team or patient will be considered a failure to tolerate the medicine.
- Number of Participants With Sustained Virologic Response [ Time Frame: 12 and 24 weeks after completing therapy ]Undetectable HDV RNA at both 12 and 24 weeks post treatment follow-up visits
- Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI) [ Time Frame: End of treatment and 24 weeks after completing therapy. ]Reduction in histologic inflammatory scores (modified HAI) by at least two points with no progression in histologic fibrosis (Ishak) at week 24 post-treatment follow-up.
- Number of Participants With Normalization of Serum ALT [ Time Frame: End of therapy, and 12 and 24 weeks after completing therapy ]Normalization of serum ALT (ALT <20 in females and ALT <31 in males) at the end of therapy, at week 12 of posttherapy follow-up and at week 24 of post-therapy follow-up, OR reduction in serum ALT by >50% of baseline at week 12 of post therapy follow up and week 24 of post therapy follow up.
- Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG) [ Time Frame: Baseline and 24 weeks after completing therapy ]Reduction in hepatic venous pressure gradient (HVPG) measurements by >25% of baseline OR normalization of HVPG (<5 mm Hg) at 24 weeks after completing therapy
- Number of Participants With Reduction in Fibroscan Transient Elastography Values [ Time Frame: Baseline and 24 weeks ]Reduction in Fibroscan transient elastography values by >25% of baseline at end of therapy.
- Number of Participants With Loss of HBsAg at Week 24 [ Time Frame: Week 24 ]Loss of HBsAg from the serum at week 24
- Number of Participants With Loss of HBsAg at Week 12 Weeks After Completing Therapy [ Time Frame: 12 weeks after completing therapy ]Loss of HBsAg from the serum at 12 weeks after completing therapy
- Number of Participants With Loss of HBsAg at 24 Weeks After Completing Therapy [ Time Frame: 24 weeks after completing therapy ]Loss of HBsAg from the serum at 24 weeks after completing therapy
- Change in Quantitative Log HBsAg Levels From Baseline to Week 24 [ Time Frame: Baseline and week 24 ]Change in quantitative log HBsAg levels at from baseline to week 24
- Change in Quantitative Log HBsAg Levels From Baseline 24 Weeks After Completing Therapy [ Time Frame: Baseline and 24 weeks after completing therapy ]Change in quantitative log HBsAg levels at from baseline to 24 weeks after completing therapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03600714
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Christopher Koh, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|