Lonafarnib With and Without Ritonavir in HDV (LOWR-1)

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
• Positive viral load by quantitative PCR
• Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval 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) 6, decompensated liver disease or any other form of non-viral hepatitis
• 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)
• any malignancy within 3 years except for basal cell skin cancer
• significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
• chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
• 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