LOWR 4: Titrating-Dose of Lonafarnib in Combination With Ritonavir

Sponsor

Eiger BioPharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02527707

Collaborator

Hannover Medical School (Other)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib in combination with ritonavir in patients chronically infected with hepatitis delta virus

Condition or Disease	Intervention/Treatment	Phase
Chronic Delta Hepatitis	Drug: lonafarnib Drug: Ritonavir	Phase 2

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 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 Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of a Titrating-Dose Lonafarnib in Combination With Ritonavir in Patients Chronically Infected With Hepatitis Delta Virus

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

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: EBP994, Sarasar Drug: Ritonavir CYP 3A4 inhibitor, lonafarnib booster Other Names: Norvir

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:

EBP994, Sarasar

Drug: Ritonavir

CYP 3A4 inhibitor, lonafarnib booster

Other Names:

Norvir

Outcome Measures

Primary Outcome Measures

Number of Patients Tolerating Dose-Escalation from Lonafarnib 50 mg bid to 75 mg bid [6 months]
Proportion of patients taking a lonafarnib dose greater than 50 mg bid at the end of the 24-week treatment period

Secondary Outcome Measures

Decrease in HDV viral load from baseline. [6 months]
change in > 2 log in HDV viral load from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Male or female, 18 to 65 years of age, inclusive
Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV RNA by qPCR at study entry
Liver biopsy demonstrating evidence of chronic hepatitis
Willingness to practice appropriate contraception

Key Exclusion Criteria:

Previous use of lonafarnib
Co-infected with HIV or HCV
Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease
Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
Evidence of another form of viral hepatitis or another form of liver disease
Evidence of hepatocellular carcinoma
Use of alpha interferon, either interferon alfa-2a or interferon alfa-2b, or pegylated interferon alfa-2a within 2 months before the start of screening
Concomitant use of any of the following:
Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
Drugs known to prolong the PR or QT interval
Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
Medications contraindicated in the prescribing information for ritonavir