Titrating-Dose of Lonafarnib in Combination With Ritonavir (LOWR-4)
Primary Purpose
Chronic Delta Hepatitis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
lonafarnib
Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Delta Hepatitis
Eligibility Criteria
Key Inclusion Criteria:
- 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 RNA by qPCR at study entry
- Liver biopsy demonstrating evidence of chronic hepatitis
- Willingness to practice appropriate contraception
Key Exclusion Criteria:
- Previous use of lonafarnib
- Co-infected with HIV or 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 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 or QT interval
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
lonafarnib/ritonavir
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Full Information
NCT ID
NCT02527707
First Posted
August 13, 2015
Last Updated
May 26, 2023
Sponsor
Eiger BioPharmaceuticals
Collaborators
Hannover Medical School
1. Study Identification
Unique Protocol Identification Number
NCT02527707
Brief Title
Titrating-Dose of Lonafarnib in Combination With Ritonavir
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
February 9, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eiger BioPharmaceuticals
Collaborators
Hannover Medical School
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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)
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Delta Hepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lonafarnib/ritonavir
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
lonafarnib
Other Intervention Name(s)
EBP994, Sarasar
Intervention Description
antiviral farnesyltransferase inhibitor
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
Norvir
Intervention Description
Cytochromes P450 3A4 inhibitor used to boost lonafarnib
Primary Outcome Measure Information:
Title
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
Description
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.
Time Frame
Baseline and Week 24 (6 months)
Secondary Outcome Measure Information:
Title
Number of Patients With 1 Log Reduction From Baseline by Timepoint
Description
Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint
Time Frame
Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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
Key Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heiner Wedemeyer, MD, PhD
Organizational Affiliation
Hannover Medical School
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
26189433
Citation
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.
Results Reference
background
PubMed Identifier
29152762
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.
Results Reference
background
PubMed Identifier
34860418
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.
Results Reference
background
Links:
URL
http://eigerbio.com
Description
Eiger BioPharmaceuticals, Inc. company website
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Titrating-Dose of Lonafarnib in Combination With Ritonavir
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