Phase 2
N=26
Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon
Liver Disease · Hepatitis D
Bottom Line
View on ClinicalTrials.gov: NCT03600714 ↗Enrolled (actual)
26
Serious AEs
0.0%
Results posted
Dec 2021
Primary outcome: Primary: Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs — 18 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Peg-interferon lambda (Drug); Lonafarnib (Drug); Ritonavir (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Primary completion
- Feb 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs |
18 | — |
| PRIMARY Number of Participants Who Discontinue Medication |
3 | — |
| SECONDARY Number of Participants With Sustained Virologic Response |
3 | — |
| SECONDARY Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI) |
6 | — |
| SECONDARY Number of Participants With Normalization of Serum ALT |
2 | — |
| SECONDARY Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG) |
10 | — |
| SECONDARY Number of Participants With Reduction in Fibroscan Transient Elastography Values |
4 | — |
| SECONDARY Number of Participants With Loss of HBsAg at Week 24 |
— | — |
| SECONDARY Number of Participants With Loss of HBsAg at Week 12 Weeks After Completing Therapy |
— | — |
| SECONDARY Number of Participants With Loss of HBsAg at 24 Weeks After Completing Therapy |
— | — |
| SECONDARY Change in Quantitative Log HBsAg Levels From Baseline to Week 24 |
0.15 | — |
| SECONDARY Change in Quantitative Log HBsAg Levels From Baseline 24 Weeks After Completing Therapy |
0.16 | — |
Summary
Background:
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.
Objectives:
To see if combining lonafarnib, ritonavir, and lambda interferon is safe and effective to treat chronic hepatitis D infection.
Eligibility:
Adults at least 18 years old with chronic hepatitis D infection
Design:
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
Eligibility Criteria
INCLUSION CRITERIA
- Age 18 years or above, male or female.
- Presence of anti-HDV in serum.
- Presence of quantifiable HDV RNA in serum at three time pre-treatment points with a mean HDV RNA level >2 log10 above the lower limit of quantification (LLOQ) of the HDV RNA assay.
- Demonstration of chronicity as evidenced by the presence of HDV RNA in serum for >/= 6 months, or presence of Anti-HDV antibody >/= 6months.
EXCLUSION CRITERIA
- Decompensated liver disease, defined by bilirubin >4mg/dL, albumin 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. Patients with an absolute neutrophil count 450 ms and/or prolonged PR interval.
- Uncontrolled elevated triglycerides (>500 mg/dL). Patients on lipid lowering therapy other than statins will be eligible for this study.
- History of pancreatitis from causes other than gallstone pancreatitis. Subjects with a baseline amylase and/or lipase level >3 ULN will be excluded from the study.
- 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.
Data sourced from ClinicalTrials.gov (NCT03600714). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.