Chronic Delta Hepatitis
Conditions
Brief summary
A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV)
Detailed description
This is a Phase 2 study of 24 weeks of treatment with a dose-titration regimen of lonafarnib/ritonavir in up to 15 patients chronically infected with HDV: lonafarnib starting at 50 mg twice daily (BID) in combination with ritonavir 100 mg BID and escalating lonafarnib as tolerated. The duration of the study for each patient is approximately 13 months (up to 4 weeks for screening, 24 weeks of treatment, 4 weeks for the primary follow-up visit, and monthly safety follow-up visits for 5 months thereafter). The 6-month follow-up after the last dose of study drug is designed to allow evaluation of the clinical and virologic course after completion of the 24-week Treatment Period.
Interventions
DRUGlonafarnib
antiviral farnesyltransferase inhibitor
DRUGRitonavir
Cytochromes P450 3A4 inhibitor used to boost lonafarnib
Sponsors
Hannover Medical School
Eiger BioPharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female, 18 to 65 years of age, inclusive 2. Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV ribonucleic acid (RNA) by quantitative polymerase chain reaction (qPCR) at study entry 3. Liver biopsy demonstrating evidence of chronic hepatitis 4. Willingness to practice appropriate contraception Key
Exclusion criteria
1. Previous use of lonafarnib 2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) 3. Active jaundice defined by total bilirubin level \>2.0 mg/dL and known not to have Gilbert's disease 4. Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy 5. Serum creatinine concentration ≥1.5 times upper limit of normal (ULN) 6. Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease 7. Evidence of hepatocellular carcinoma 8. Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening 9. Concomitant use of any of the following: 1. Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19 2. Drugs known to prolong the PR interval or QT interval of the electrocardiogram 3. Receipt of systemic immunosuppressive therapy within the 3 months before start of screening 4. Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation 5. Medications contraindicated in the prescribing information for ritonavir
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer | Baseline and Week 24 (6 months) | Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With 1 Log Reduction From Baseline by Timepoint | Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24 | Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lonafarnib/Ritonavir Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up.
lonafarnib: antiviral farnesyltransferase inhibitor
Ritonavir: Cytochromes P450 3A4 inhibitor used to boost lonafarnib | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Lonafarnib/Ritonavir |
|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID.
Time frame: Baseline and Week 24 (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lonafarnib/Ritonavir | Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer | -1.62 log IU/mL | Standard Deviation 1.4 |
Secondary
Number of Patients With 1 Log Reduction From Baseline by Timepoint
Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint
Time frame: Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 1 | 7 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 2 | 6 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 4 | 10 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 6 | 11 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 8 | 10 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 12 | 12 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 16 | 12 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 20 | 10 Participants |
| Lonafarnib/Ritonavir | Number of Patients With 1 Log Reduction From Baseline by Timepoint | Week 24 | 9 Participants |