Once Daily Dosing of Lonafarnib Co-administered With Ritonavir for Treatment of Chronic Hepatitis D Virus Infection

Inclusion Criteria: 1. Chronic HDV infection, with compensated liver disease, documented by a positive HDV antibody (Ab) test and HDV RNA by quantitative polymerase chain reaction (qPCR) assay, prior to initiation of trial treatment. 2. Demonstrable suppression of HBV DNA (\< 100 IU/mL) following anti-HBV nucleos(t)ide treatment prior to initiating trial therapy. 3. Willing and able to comply with trial procedures and provide written informed consent. 4. ALT \> ULN documented on at least one occasion during the 12 months preceding enrollment to the trial. 5. Male and female participants who are 18 years of age or above. 6. ECGs demonstrating no acute ischemia or clinically significant (CS) abnormality and a corrected QT interval by Fridericia correction formula (QTcF) \< 450 ms in males and \<470 ms in females. 7. Sexually active female patients of childbearing potential and sexually active male patients with partners of childbearing potential must agree to use adequate methods of contraception during the trial. Females of childbearing potential are all those except women who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal. For female patients: * Progestin-based hormonal contraception (implant, injection, oral) associated with inhibition of ovulation for ≥ 3 months before screening. Use of a progestin-based implant or injection method requires the additional use of a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening. Use of a progestin-only, oral method requires the additional use of double barrier methods (use of condom \[male partner\] with either diaphragm with spermicide or cervical cap with spermicide) from screening, or * Intrauterine device (IUD) or intrauterine system (IUS) in place ≥ 3 months before screening AND a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening, or * Surgical sterilization of the partner (vasectomy ≥ 1 month before screening) AND a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening, or * Double-barrier methods (use of condom \[male partner\] with either diaphragm with spermicide or cervical cap with spermicide) from screening. For male patients: * Surgical sterilization (vasectomy ≥ 1 month before screening) AND a barrier method (use of condom or diaphragm with spermicide or cervical cap with spermicide) from screening, or * Consistently and correctly use a condom from screening AND female partner must agree to use a hormonal contraceptive, a nonhormonal non-barrier method (eg, copper IUD), or a nonhormonal barrier method (eg, diaphragm with spermicide or cervical cap with spermicide). Exclusion Criteria: 1. Participation in a clinical trial with, or use of, any investigational agent within 30 days or 5 half-lives, whichever is longer, before starting LNF treatment. 2. Female patients who are pregnant or breastfeeding. Female patients must have a negative serum test at screening and a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[hCG\] at baseline, within 24 hours prior to the start of any investigational agent). Male patients with female sexual partners who are pregnant. 3. Current or previous history of decompensated liver disease (e.g. variceal bleeding, ascites, hepatic encephalopathy, hepatorenal syndrome). 4. Platelet count \< 70,000 cells/mm3; white blood cell (WBC) \< 3,000 cells / mm3 5. Creatinine clearance (\< 30 mL/min by Cockroft-Gault). 6. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Patients with a positive HCV Ab at baseline are allowed if they have completed a curative antiviral regimen and have documented undetectable HCV RNA 12 weeks or more following last dose of anti-HCV medications. 7. Abnormal thyroid-stimulating hormone (TSH) or free thyroxine (fT4) levels. Patients with well-controlled thyroid function or TFTs that are not clinically significant may be enrolled. 8. Evidence of another form of viral hepatitis or another form of liver disease (eg, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, alcoholic liver disease, nonalcoholic steatohepatitis, hemochromatosis, alpha 1 anti-trypsin deficiency). 9. History of hepatocellular carcinoma. 10. Retinal disorder or clinically relevant ophthalmic disorder 11. Any malignancy within 5 preceding years. Exceptions are malignancies surgically excised with curative intent and/or evidence of being disease free for at least 5 years (eg, breast ductal carcinoma in situ \[DCIS\] or squamous/basal cell skin cancer treated with curative intent), or successfully treated in-situ carcinoma of the cervix 12. Other significant medical condition that may require intervention during the trial. 13. Any condition that may impact proper absorption (eg, short bowel syndrome, inflammatory bowel disease, atrophic gastritis, partial gastrectomy) should be discussed with the Medical Monitor. 14. Consumption of grapefruit, Seville oranges, or product that contains grapefruit or Seville oranges. 15. Use of heparin or warfarin during the trial. 16. Long-term treatment (\> 2 weeks) before or during the trial with agents that have a high risk for nephrotoxicity or hepatotoxicity. 1. Concomitant use (within 2 weeks of Day 1 and throughout trial conduct) of any medications (prescription, OTC, herbal products) or foods as follows: 2. Known potent inhibitors of CYP3A, including statins (with the exception of pravastatin and fluvastatin); 3. Known potent inducers of CYP3A or CYP3A sensitive substrates; 4. Known CYP2C19 and P-gp sensitive substrates with a narrow therapeutic index - refer to the Concomitant Medication Manual for additional instructions; 5. Known sensitive substrates of OCT1 with a narrow therapeutic index; and 6. Drugs known to prolong the PR or QT interval unless otherwise described in this protocol. 17. Concomitant use of medications contraindicated in the prescribing information for RTV.