Lonafarnib Boosted With Ritonavir With and Without Peginterferon Alfa-2a (PEG IFN-a) in HDV (LOWR-2) (LOWR-2)

March 1, 2023 updated by: Eiger BioPharmaceuticals

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)

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).

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. Up to sixty subjects with chronic delta hepatitis will be randomized to receive one of ten different doses of lonafarnib. Dosing will occur over 12-48 weeks, 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 nine dosing combinations of lonafarnib with ritonavir boosting with and without peginterferon alfa-2a (PEG IFN-a).

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

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

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 (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:

    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
Intervention / Treatment
Experimental: lonafarnib/ritonavir - I
lonafarnib 100 mg BID + ritonavir 100 mg QD
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir - II
lonafarnib 100 mg BID + ritonavir 50 mg BID
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir - III
lonafarnib 100 mg QD + ritonavir 100 mg QD
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir - IV
lonafarnib 150 mg QD + ritonavir 100 mg QD
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir/PEG IFN-a - V
lonafarnib 75 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Drug: Pegylated interferon-alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-a
  • Peginterferon alfa-2a
  • PEG IFN-alfa-2a
Experimental: lonafarnib/ritonavir - VI
lonafarnib 25 mg BID + ritonavir 100 mg BID
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir - VII
lonafarnib 50 mg BID + ritonavir 100 mg BID
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Experimental: lonafarnib/ritonavir/PEG IFN-a - VIII
lonafarnib 50 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Drug: Pegylated interferon-alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-a
  • Peginterferon alfa-2a
  • PEG IFN-alfa-2a
Experimental: lonafarnib/ritonavir/PEG IFN-a - IX
lonafarnib 25 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Drug: Pegylated interferon-alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-a
  • Peginterferon alfa-2a
  • PEG IFN-alfa-2a
Experimental: lonafarnib/ritonavir/PEG IFN-a - X
lonafarnib 50 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Names:
  • Sarasar, EBP994, LNF
Drug: ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Names:
  • Norvir, RTV
Drug: Pegylated interferon-alfa-2a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-a
  • Peginterferon alfa-2a
  • PEG IFN-alfa-2a

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT)
Time Frame: 12-48 weeks
Proportion of intent to treat patients with ≥2 log10 decline of HDV RNA from baseline at end of treatment (EOT)
12-48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
< LLOQ in HDV RNA at End of Treatment (EOT)
Time Frame: 12-48 weeks
Proportion of intent to treat patients with HDV RNA below the limit of quantitation at end of treatment
12-48 weeks
ALT Normalization at End of Treatment
Time Frame: 12-48 weeks
Proportion of intent to treat population who normalize ALT at end of treatment
12-48 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean HDV RNA Decline
Time Frame: 12-48 weeks
mean HDV RNA decline of intent to treat population from baseline to end of treatment
12-48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eiger BioPharmaceuticals

Collaborators

Ankara University

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.

General Publications

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 (Actual)

December 1, 2014

Primary Completion (Actual)

April 18, 2017

Study Completion (Actual)

June 15, 2017

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)

March 3, 2023

Last Update Submitted That Met QC Criteria

March 1, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EIG-300-Amendment 3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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