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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Turkey
      • Ankara, Turkey
        • Ankara University Medical School

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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:

    1. abstinence
    2. surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum
    3. IUD in place for at least six months
    4. barrier methods (condom or diaphragm) with spermicide
    5. surgical sterilization of the partner (vasectomy for six months)
    6. 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:

    1. variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6, decompensated liver disease or any other form of non-viral hepatitis
    2. 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)
    3. any malignancy within 3 years except for basal cell skin cancer
    4. significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
    5. chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
    6. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: lonafarnib - I
lonafarnib 200 mg BID; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Experimental: lonafarnib - II
lonafarnib 300 mg BID; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Experimental: lonafarnib - III
lonafarnib 100 mg TID; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Experimental: lonafarnib/PEG IFN-a - I
lonafarnib 100 mg BID + PEG IFN-a 180 ug QW; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Drug: peginterferon alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • pegylated interferon-alfa
  • PEG IFN-alfa
  • PEG IFN-a
Experimental: lonafarnib/PEG IFN-a - II
lonafarnib 200 mg BID + PEG IFN-a 180 ug QW; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Drug: peginterferon alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • pegylated interferon-alfa
  • PEG IFN-alfa
  • PEG IFN-a
Experimental: lonafarnib/PEG IFN-a - III
lonafarnib 300 mg BID + PEG IFN-a 180 ug QW; n=2
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Drug: peginterferon alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • pegylated interferon-alfa
  • PEG IFN-alfa
  • PEG IFN-a
Experimental: lonafarnib/ritonavir
lonafarnib 100 mg BID + ritonavir 100 mg QD; n=3
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir
  • RTV

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eiger BioPharmaceuticals

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 30, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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