Titrating-Dose of Lonafarnib in Combination With Ritonavir (LOWR-4)

May 26, 2023 updated by: Eiger BioPharmaceuticals

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2

Expanded Access

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

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Male or female, 18 to 65 years of age, inclusive
  2. 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
  3. Liver biopsy demonstrating evidence of chronic hepatitis
  4. Willingness to practice appropriate contraception

Key Exclusion Criteria:

  1. Previous use of lonafarnib
  2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
  3. Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease
  4. Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
  5. Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
  6. Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease
  7. Evidence of hepatocellular carcinoma
  8. Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening

  9. Concomitant use of any of the following:

    1. Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
    2. Drugs known to prolong the PR interval or QT interval of the electrocardiogram
    3. Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
    4. Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
    5. Medications contraindicated in the prescribing information for ritonavir

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: lonafarnib/ritonavir
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.
Drug: lonafarnib
antiviral farnesyltransferase inhibitor
Other Names:
  • Sarasar
  • EBP994
Drug: Ritonavir
Cytochromes P450 3A4 inhibitor used to boost lonafarnib
Other Names:
  • Norvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
Time Frame: Baseline and Week 24 (6 months)
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.
Baseline and Week 24 (6 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With 1 Log Reduction From Baseline by Timepoint
Time Frame: Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint
Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24

Collaborators and Investigators

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

Sponsor

Eiger BioPharmaceuticals

Collaborators

Hannover Medical School

Investigators

  • Principal Investigator: Heiner Wedemeyer, MD, PhD, Hannover Medical School

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

September 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

February 9, 2017

Study Registration Dates

First Submitted

August 13, 2015

First Submitted That Met QC Criteria

August 17, 2015

First Posted (Estimated)

August 19, 2015

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

May 26, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EIG-LNF-002

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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