A clinical study to assess the efficacy and safety of the investigational drug Lonafarnib in combination with Ritonavir in patients with chronic infection with the Hepatitis Delta Virus receiving long-term anti-HBV therapy with nucleos(t)ides (D-LIVR)

Belgium, Bulgaria, Canada, France, Germany, Greece, Israel, Italy, Moldova, Republic of, Mongolia, New Zealand, Pakistan, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States, Vietnam (ICTRP)

Identifiant de l'essai ICTRP
NCT03719313 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
non disponible

Titre académique
A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID With and Without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared With PEG IFN-alfa-2a Monotherapy and Placebo Treatment in Patients Chronically Infected With Hepatitis Delta Virus Being Maintained on Anti-HBV Nucleos(t)Ide Therapy (D-LIVR) (ICTRP)

Titre public
Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a (ICTRP)

Maladie en cours d'investigation
Hepatitis Delta Virus (ICTRP)

Intervention étudiée
Drug: Lonafarnib;Drug: Ritonavir;Drug: PEG IFN-alfa-2a;Drug: Placebo Lonafarnib;Drug: Placebo Ritonavir (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Critères d'inclusion/exclusion
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.
(ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.;To compare the composite virologic and biochemical response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo. (ICTRP)

To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.;To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.;To evaluate the health-related quality of life (HRQL) over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo.;To evaluate the HRQL over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo.;To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo.;To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo. (ICTRP)

Date d'enregistrement
18.10.2018 (ICTRP)

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Sue Speyer, DLIVR@eigerbio.com, 650-272-6138 (ICTRP)

ID secondaires
EIG-LNF-011 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/show/NCT03719313 (ICTRP)