Titrating-Dose of Lonafarnib in Combination With Ritonavir
Titrating-Dose of Lonafarnib in Combination With Ritonavir
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
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.
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 RNA by 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 HIV or 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 or another form of liver disease

 7. Evidence of hepatocellular carcinoma

 8. 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

 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 or QT interval

 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