Titrating-Dose of Lonafarnib in Combination With Ritonavir

Chronic Delta Hepatitis Clinical Trial

— LOWR-4  

Official title:

A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of a Titrating-Dose Lonafarnib/Ritonavir in Patients Chronically Infected With Hepatitis Delta Virus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527707
• Other study ID #: EIG-LNF-002
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: February 9, 2017

Study information

• Verified date: May 2023
• Source: Eiger BioPharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV)

Description:

This is a Phase 2 study of 24 weeks of treatment with a dose-titration regimen of lonafarnib/ritonavir in up to 15 patients chronically infected with HDV: lonafarnib starting at 50 mg twice daily (BID) in combination with ritonavir 100 mg BID and escalating lonafarnib as tolerated. The duration of the study for each patient is approximately 13 months (up to 4 weeks for screening, 24 weeks of treatment, 4 weeks for the primary follow-up visit, and monthly safety follow-up visits for 5 months thereafter). The 6-month follow-up after the last dose of study drug is designed to allow evaluation of the clinical and virologic course after completion of the 24-week Treatment Period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 9, 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

1. Male or female, 18 to 65 years of age, inclusive

2. Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV ribonucleic acid (RNA) by quantitative polymerase chain reaction (qPCR) at study entry

3. Liver biopsy demonstrating evidence of chronic hepatitis

4. Willingness to practice appropriate contraception

Key Exclusion Criteria:

1. Previous use of lonafarnib

2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)

3. Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease

4. Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy

5. Serum creatinine concentration =1.5 times upper limit of normal (ULN)

6. Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease

7. Evidence of hepatocellular carcinoma

8. Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening

9. Concomitant use of any of the following:

1. Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19

2. Drugs known to prolong the PR interval or QT interval of the electrocardiogram

3. Receipt of systemic immunosuppressive therapy within the 3 months before start of screening

4. Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation

5. Medications contraindicated in the prescribing information for ritonavir

Related Conditions & MeSH terms

• Chronic Delta Hepatitis
• Hepatitis
• Hepatitis D
• Hepatitis D, Chronic

Intervention

Drug:
• lonafarnib
antiviral farnesyltransferase inhibitor
• Ritonavir
Cytochromes P450 3A4 inhibitor used to boost lonafarnib

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Eiger BioPharmaceuticals	Hannover Medical School

References & Publications (3)

Koh C, Canini L, Dahari H, Zhao X, Uprichard SL, Haynes-Williams V, Winters MA, Subramanya G, Cooper SL, Pinto P, Wolff EF, Bishop R, Ai Thanda Han M, Cotler SJ, Kleiner DE, Keskin O, Idilman R, Yurdaydin C, Glenn JS, Heller T. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015 Oct;15(10):1167-1174. doi: 10.1016/S1473-3099(15)00074-2. Epub 2015 Jul 16. — View Citation

Yurdaydin C, Keskin O, Kalkan C, Karakaya F, Caliskan A, Karatayli E, Karatayli S, Bozdayi AM, Koh C, Heller T, Idilman R, Glenn JS. Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study. Hepatology. 2018 Apr;67(4):1224-1236. doi: 10.1002/hep.29658. Epub 2018 Feb 19. — View Citation

Yurdaydin C, Keskin O, Yurdcu E, Caliskan A, Onem S, Karakaya F, Kalkan C, Karatayli E, Karatayli S, Choong I, Apelian D, Koh C, Heller T, Idilman R, Bozdayi AM, Glenn JS. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology. 2022 Jun;75(6):1551-1565. doi: 10.1002/hep.32259. Epub 2021 Dec 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer	Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID.	Baseline and Week 24 (6 months)
Secondary	Number of Patients With 1 Log Reduction From Baseline by Timepoint	Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint	Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24

External Links

•   Eiger BioPharmaceuticals, Inc. company website