Lonafarnib Boosted With Ritonavir With and Without Peginterferon Alfa-2a (PEG IFN-a) in HDV (LOWR-2)
LOWR-2
An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir-Boosting +/- Peginterferon Alfa-2a in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-2)
1 other identifier
interventional
55
1 country
1
Brief Summary
An Open-label, Dose-ranging Study to Evaluate the Safety and Efficacy of Lonafarnib with Ritonavir Boosting +/- Peginterferon alfa-2a in Patients Chronically Infected with Delta Hepatitis (HDV) (LOWR-2).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2014
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2014
CompletedFirst Submitted
Initial submission to the registry
April 21, 2015
CompletedFirst Posted
Study publicly available on registry
April 30, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 18, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
June 15, 2017
CompletedResults Posted
Study results publicly available
February 21, 2023
CompletedMarch 3, 2023
March 1, 2023
2.4 years
April 21, 2015
January 24, 2023
March 1, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT)
Proportion of intent to treat patients with ≥2 log10 decline of HDV RNA from baseline at end of treatment (EOT)
12-48 weeks
Secondary Outcomes (2)
< LLOQ in HDV RNA at End of Treatment (EOT)
12-48 weeks
ALT Normalization at End of Treatment
12-48 weeks
Other Outcomes (1)
Mean HDV RNA Decline
12-48 weeks
Study Arms (10)
lonafarnib/ritonavir - I
EXPERIMENTALlonafarnib 100 mg BID + ritonavir 100 mg QD
lonafarnib/ritonavir - II
EXPERIMENTALlonafarnib 100 mg BID + ritonavir 50 mg BID
lonafarnib/ritonavir - III
EXPERIMENTALlonafarnib 100 mg QD + ritonavir 100 mg QD
lonafarnib/ritonavir - IV
EXPERIMENTALlonafarnib 150 mg QD + ritonavir 100 mg QD
lonafarnib/ritonavir/PEG IFN-a - V
EXPERIMENTALlonafarnib 75 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
lonafarnib/ritonavir - VI
EXPERIMENTALlonafarnib 25 mg BID + ritonavir 100 mg BID
lonafarnib/ritonavir - VII
EXPERIMENTALlonafarnib 50 mg BID + ritonavir 100 mg BID
lonafarnib/ritonavir/PEG IFN-a - VIII
EXPERIMENTALlonafarnib 50 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
lonafarnib/ritonavir/PEG IFN-a - IX
EXPERIMENTALlonafarnib 25 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
lonafarnib/ritonavir/PEG IFN-a - X
EXPERIMENTALlonafarnib 50 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
Interventions
antiviral farnesyl transferase inhibitor
CYP 3A4 inhibitor, lonafarnib booster
immunomodulator
Eligibility Criteria
You may qualify if:
- Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR
- Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry
- Liver biopsy within the last two years (biopsy can be done at the Screening Visit)
- Positive viral load of \>100,000 copies/mL as measured by quantitative PCR
- Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval \<450 milliseconds - using Bazett's correction
- Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study:
- abstinence
- surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum
- IUD in place for at least six months
- barrier methods (condom or diaphragm) with spermicide
- surgical sterilization of the partner (vasectomy for six months)
- hormonal contraceptives for at least three months prior to the first dose of study drug
- Willing and able to comply with study procedures and provide written informed consent
You may not qualify if:
- Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1
- Patients co-infected with HIV
- Patients with screening tests positive for HCV, or anti-HIV Ab
- History of decompensated cirrhosis within the past year
- Active jaundice defined by total bilirubin \> 2.0 excluding Gilbert's disease
- INR ≥ 1.5
- Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (\> 20 g per day for females (1.5 standard alcohol drinks) or \> 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL)
- Drug abuse within the last six months with the exception of cannabinoids and their derivatives
- Patients with absolute neutrophil count (ANC) \< 1500 cells/mm\^3; platelet count \< 100,000 cells/mm\^3; hemoglobin \< 12 g/dL for women and \< 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN)
- History or clinical evidence of any of the following:
- variceal bleeding, ascites, hepatic encephalopathy, CTP score \> 6, decompensated liver disease or any other form of non-viral hepatitis
- immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent nonsteroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed)
- any malignancy within 3 years except for basal cell skin cancer
- significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
- chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eiger BioPharmaceuticalslead
- Ankara Universitycollaborator
Study Sites (1)
Ankara University Medical School
Ankara, Turkey (Türkiye)
Related Publications (1)
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: 34860418DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior VP, Clinical Development
- Organization
- Eiger BioPharmaceuticals, Inc.
Study Officials
- PRINCIPAL INVESTIGATOR
Cihan Yurdaydin, MD
Ankara University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
April 21, 2015
First Posted
April 30, 2015
Study Start
December 1, 2014
Primary Completion
April 18, 2017
Study Completion
June 15, 2017
Last Updated
March 3, 2023
Results First Posted
February 21, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will not share