Chronic Hepatitis D Virus (HDV) Infection.
Conditions
Interventions
Product Name: Lonafarnib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lonafarnip
CAS Number: 193275-84-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Eiger BioPharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient may be included in this study if he or she meets all of the following criteria: 1. Willing and able to comply with study procedures and provide written informed consent. 2. Male or female, 18 to 65 years of age, inclusive. 3. Has a body mass index (BMI) of =18 kg/m2 and has a body weight of =45 kg. 4. Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV RNA by qPCR at study entry. 5. Liver biopsy demonstrating evidence of chronic hepatitis. If no liver biopsy is available, the patient must be willing to consent to and have no contraindication to liver biopsy. Liver biopsy will be performed during screening. 6. ALT =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Participation in a trial with or use of any investigational agent within 30 days of start of screening 2. Pregnant or lactating/breastfeeding 3. Previous use of lonafarnib 4. Co-infected with HIV or active infection with HCV 5. Positive results for HIV or HCV Ab at screening. Patients with positive HCV Ab at screening are allowed if they have completed a curative antiviral regimen and are documented to be HCV RNA negative (undetectable) at least 3 months before and at screening 6. Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilberts disease 7. A CPT score of >6-based on screening lab results 8. Decompensated liver disease or cirrhosis as defined by the presence of any of the following on screening lab tests: a. Bilirubin level >2.0 mg/dL b. Albumin level 20 g/day for females (1.5 standard alcohol drinks) or >30 g/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) 15. In the opinion of the Investigator, an alcohol use pattern that will interfere with study conduct 16. Drug abuse within the previous 6 months before the screening visit with the exception of medically prescribed cannabinoids and their derivatives 17. History or clinical evidence of any of the following: a. Immunologically mediated disease that requires more than intermittent nonsteroidal anti-inflammatory medications for management or that requires use of systemic corticosteroids in prior 6 months b. History of or evidence of retinal disorder or clinically relevant ophthalmic disorder c. Any malignancy within 5 years of the start of screening. Exceptions are superficial dermatologic malignancies d. Significant or unstable cardiac disease e. Chronic pulmonary disease associated with functional impairment f. Pancreatitis g. Severe or uncontrolled psychiatric disease, incl severe depression, history of suicidal ideation, suicidal attempts, or psychosis requiring medication and/or hospitalization 18. Solid organ transplantation, incl liver 19. Use of alpha interferon, either interferon alfa-2a or interferon alfa-2b, or pegylated interferon alfa-2a or pegylated interferon alfa-2b within 2 months before the start of screening 20. Concomitant use of any of the following: a. Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19 b. Drugs known to prolong the PR or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are to - Evaluate the safety and tolerability of the following dose-titration regimen of lonafarnib in combination with ritonavir over the 24-week Treatment Period: * lonafarnib/ritonavir starting at 50 mg bid/100 mg twice daily (bid) and escalated to * lonafarnib/ritonavir 75 mg bid/100 mg bid and then to 100 mg bid/100 mg bid as tolerated ? - Evaluate the pharmacodynamic activity (change in hepatitis D viral [HDV] load) of the dose-titration regimen of lonafarnib in combination with ritonavir over the 24-week Treatment Period;Secondary Objective: The secondary objectives of the study are to evaluate the effect of the dose-titration regimen of lonafarnib/ritonavir on the following: - Pharmacokinetics (PK) - Change in alanine aminotransferase (ALT) levels - Change in hepatitis B virus (HBV) DNA levels Exploratory objectives of the study are to evaluate the effects of the dose-titration regimen of lonafarnib/ritonavir on immunologic parameters during treatment.;Primary end point(s): The purpose of this study is to evaluate the safety and tolerability of the dose-titration regimen of lonafarnib in combination with ritonavir over the 24-week treatment period. ;Timepoint(s) of evaluation of this end point: Week 0 (Day 1), Week 1 (Day 8 ± 2 d), Week 2 (Day 15 ± 2 d), Week 4 (Day 29 ± 2 d), Week 6 (Day 43 ± 2 d), Week 8 (Day 57 ± 5 d), Week 12 (Day 85 ± 5 d), Week 16 (Day 113 ± 5 d), Week 20 (Day 141 ± 5 d), and Week 24 (Day 169 ± 5 d). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In addition, the PD activity (ie, change in HDV viral load) of the lonafarnib/ritonavir dose-titration regimen over the 24-week Treatment Period will be evaluated. Secondary evaluations will include the effect the lonafarnib/ritonavir dose-titration regimen on PK characteristics, ALT levels, and HBV DNA levels. Exploratory evaluations will include the effects of the lonafarnib/ritonavir dose-titration regimen on immunologic parameters during treatment.;Timepoint(s) of evaluation of this end point: Week 0 (Day 1), Week 1 (Day 8 ± 2 d), Week 2 (Day 15 ± 2 d), Week 4 (Day 29 ± 2 d), Week 6 (Day 43 ± 2 d), Week 8 (Day 57 ± 5 d), Week 12 (Day 85 ± 5 d), Week 16 (Day 113 ± 5 d), Week 20 (Day 141 ± 5 d), and Week 24 (Day 169 ± 5 d). | — |
Countries
Germany
Contacts
Public ContactChief Medical Officer
Eiger BioPharmaceuticals
Outcome results
None listed