Titrating-Dose of Lonafarnib in Combination With Ritonavir

NCT02527707 | Completed Phase 2 Results DMC

• 1 other identifier: EIG-LNF-002
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Chronic Delta Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Patients With 1 Log Reduction From Baseline by Timepoint

  Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24

Study Arms (1)

lonafarnib/ritonavir

EXPERIMENTAL

Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up.

Drug: lonafarnib; Drug: Ritonavir

Interventions

lonafarnib DRUG

antiviral farnesyltransferase inhibitor

Also known as: EBP994, Sarasar

lonafarnib/ritonavir

Ritonavir DRUG

Cytochromes P450 3A4 inhibitor used to boost lonafarnib

Also known as: Norvir

lonafarnib/ritonavir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 to 65 years of age, inclusive
• 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
• Liver biopsy demonstrating evidence of chronic hepatitis
• Willingness to practice appropriate contraception

You may not qualify if:

• Previous use of lonafarnib
• Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
• Active jaundice defined by total bilirubin level \>2.0 mg/dL and known not to have Gilbert's disease
• Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
• Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
• Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease
• Evidence of hepatocellular carcinoma
• Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening
• Concomitant use of any of the following:
• Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
• Drugs known to prolong the PR interval or QT interval of the electrocardiogram
• Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
• Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
• Medications contraindicated in the prescribing information for ritonavir

Sponsors & Collaborators

• Eiger BioPharmaceuticals: lead
• Hannover Medical School: collaborator

Related 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.

  PMID: 26189433 BACKGROUND

• 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.

  PMID: 29152762 BACKGROUND

• 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.

  PMID: 34860418 BACKGROUND

Related Links

• Eiger BioPharmaceuticals, Inc. company website

MeSH Terms

Conditions

Hepatitis D, Chronic

Interventions

lonafarnib; Ritonavir

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: SVP Clinical Development
• Organization: Eiger BioPharmaceuticals, Inc.

info@eigerbio.com

1-650-272-6138

Study Officials

• Heiner Wedemeyer, MD, PhD

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: August 19, 2015
• Study Start: September 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: February 9, 2017
• Last Updated: June 22, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-05