- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02430181
Lonafarnib With and Without Ritonavir in HDV (LOWR-1) (LOWR-1)
November 3, 2022 updated by: Eiger BioPharmaceuticals
An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With and Without Ritonavir Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-1)
To Evaluate the Safety and Efficacy of Lonafarnib with and without Ritonavir Boosting in Adults With Genotype 1 Chronic Hepatitis D Virus (HDV) Infection (LOWR-1).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Chronic delta hepatitis is a serious form of chronic liver disease caused by infection with the hepatitis D virus (HDV), a small RNA virus that requires farnesylation of its major structural protein (HDV antigen) for replication.
Twenty-one subjects with chronic delta hepatitis will be randomized to receive one of seven different doses of lonafarnib.
Dosing will occur over 4-12 weeks, depending on treatment arm, and during that time, evidence of antiviral response will be assessed by frequent measurements of HDV-RNA.
The primary therapeutic endpoint will be an improvement in quantitative serum HDV RNA levels after treatment with lonafarnib therapy.
The primary safety endpoint will be the ability to tolerate the drug at the prescribed dose for the treatment duration.
Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms.
Therapy will be stopped for intolerance to lonafarnib.
This study is designed as a phase 2a study assessing the safety, tolerance and antiviral activity of seven dose combinations of lonafarnib with and without ritonavir boosting.
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ankara, Turkey
- Ankara University Medical School
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
- Positive viral load 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
Exclusion Criteria:
- 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
- severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization 2
- Patients with a body mass index > 30 kg/m^2
- Concomitant drugs known to prolong the QT interval
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: lonafarnib - I
lonafarnib 200 mg BID; n=3
|
antiviral farnesyl transferase inhibitor
Other Names:
|
Experimental: lonafarnib - II
lonafarnib 300 mg BID; n=3
|
antiviral farnesyl transferase inhibitor
Other Names:
|
Experimental: lonafarnib - III
lonafarnib 100 mg TID; n=3
|
antiviral farnesyl transferase inhibitor
Other Names:
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Experimental: lonafarnib/PEG IFN-a - I
lonafarnib 100 mg BID + PEG IFN-a 180 ug QW; n=3
|
antiviral farnesyl transferase inhibitor
Other Names:
immunomodulator
Other Names:
|
Experimental: lonafarnib/PEG IFN-a - II
lonafarnib 200 mg BID + PEG IFN-a 180 ug QW; n=3
|
antiviral farnesyl transferase inhibitor
Other Names:
immunomodulator
Other Names:
|
Experimental: lonafarnib/PEG IFN-a - III
lonafarnib 300 mg BID + PEG IFN-a 180 ug QW; n=2
|
antiviral farnesyl transferase inhibitor
Other Names:
immunomodulator
Other Names:
|
Experimental: lonafarnib/ritonavir
lonafarnib 100 mg BID + ritonavir 100 mg QD; n=3
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antiviral farnesyl transferase inhibitor
Other Names:
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Improvement in Quantitative Serum HDV RNA Levels After 4-12 Weeks of Lonafarnib-based Therapy
Time Frame: 4-12 weeks
|
log HDV RNA decline from baseline to end of treatment (4-12 weeks of lonafarnib-based therapy)
|
4-12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2014
Primary Completion (Actual)
September 1, 2015
Study Completion (Actual)
November 1, 2015
Study Registration Dates
First Submitted
April 21, 2015
First Submitted That Met QC Criteria
April 25, 2015
First Posted (Estimate)
April 30, 2015
Study Record Updates
Last Update Posted (Actual)
November 29, 2022
Last Update Submitted That Met QC Criteria
November 3, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Liver Diseases
- Hepatitis, Viral, Human
- Hepatitis, Chronic
- Hepatitis
- Hepatitis D
- Hepatitis D, Chronic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Interferons
- Interferon-alpha
- Peginterferon alfa-2a
- Ritonavir
- Lonafarnib
Other Study ID Numbers
- EIG-300
- Application #1128309 (Other Identifier: Turkish Regulatory Authority)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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