Eine klinische Studie zur Beurteilung der Wirksamkeit und Sicherheit des Prüfmedikaments Lonafarnib bei gleichzeitiger Gabe mit Ritonavir bei Patienten mit chronischer Infektion mit dem Hepatitis-Delta-Virus, die eine Anti-HBV-Langzeittherapie mit Nukleos(t)iden erhalten (D-LIVR)

Drug: Lonafarnib;Drug: Ritonavir;Drug: PEG IFN-alfa-2a;Drug: Placebo Lonafarnib;Drug: Placebo Ritonavir

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

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.

2. 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.

3. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.

4. Baseline liver biopsy demonstrating evidence of chronic hepatitis.

5. ECGs demonstrating no acute ischemia or clinically significant abnormality.

6. Normal dilated retinal examination.

Exclusion Criteria:

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-a (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.