Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a

Open to people ages 18 years and up

1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV antibody test and HDV RNA ≥ 500 IU/mL.

Note: All genotypes of HDV permitted.

1. Demonstrable suppression of HBV DNA following at least 12 weeks of anti-HBV nucleos(t)ide treatment with entecavir or tenofovir prior to initiating therapy.
2. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.
3. Baseline liver biopsy demonstrating evidence of chronic hepatitis.
4. ECGs demonstrating no acute ischemia or clinically significant abnormality.
5. Normal dilated retinal examination.

General Exclusions

1. Previous use of LNF within 12 months.
2. Current or previous history of decompensated liver disease.
3. Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable HIV RNA and HCV RNA, respectively.
4. Evidence of significant portal hypertension.
5. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.
6. History of hepatocellular carcinoma.
7. Patients with any of the following:
   • Current eating disorder
   • Evidence of alcohol substance use disorder.
   • Drug abuse within the previous 6 months before screening.
8. Prior history or current evidence of any of the following:
   • Immunologically mediated disease,
   • Retinal disorder or clinically relevant ophthalmic disorder,
   • Any malignancy within 5 years before screening,
   • Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease,
   • Chronic pulmonary disease,
   • Pancreatitis or colitis,
   • Severe or uncontrolled psychiatric disorder.
9. Other significant medical condition that may require intervention during the study.
10. Any condition that may impact proper absorption.
11. Therapy with an immunomodulatory agent, IFN-α (eg, IFN alfa-2a or IFN-alfa-2b, or pegylated IFN-alfa-2a or alfa 2b), cytotoxic agent, or chronic systemic corticosteroids within 12 months of screening.
12. Use of heparin or warfarin.
13. Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV.
14. Receipt of systemic immunosuppressive therapy.
15. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir.