Clinical Trials List
Protocol NumberEIG-LNF-011
2019-10-01 - 2023-07-17
Phase III
Recruiting6
ICD-10B17.0
Acute delta-(super) infection of hepatitis B carrier
ICD-9070.52
Hepatitis delta without mention of active hepatitis B disease without mention of hepatic coma
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)
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Eiger BioPharmaceuticals, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chun-Yen Lin 未分科
- Wen-Juei Jeng 未分科
- I-Shyan Sheen 未分科
- Rong-Nan Chien Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jee-Fu Huang 未分科
- Ming-Lung Yu 未分科
- Chia-Yen Dai 未分科
- Chung-Feng Huang 未分科
- Ming-Lun Yeh 未分科
- 黃駿逸 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
D-LIVR
Objectives
The primary objectives are as follows:
• To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) (Week 48) 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 (Week 48) in patients who receive
LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.
Test Drug
Lonafarnib
Active Ingredient
Lonafarnib
Dosage Form
capsule
Dosage
25
Endpoints
Efficacy:
Efficacy will be assessed by HDV RNA viral load, ALT levels, HBV DNA and serology, liver biopsy, FibroScan® and/or FibroTest results, and Chronic Liver Disease Questionnaire (CLDQ) results. Possible future exploratory efficacy parameters include HDV RNA sequencing for patients with non-response or HDV RNA rebound on therapy.
Safety:
To assess the safety and tolerability of the study drugs, the following will be monitored: adverse events (AEs), clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, physical examinations, ophthalmological assessments, semen analyses (as applicable), electrocardiograms (ECGs), concomitant medications, and depression (as applicable). In addition, to monitor the safety of the anti-HBV nucleotide, tenofovir, bone density will be monitored for some patients.
Efficacy will be assessed by HDV RNA viral load, ALT levels, HBV DNA and serology, liver biopsy, FibroScan® and/or FibroTest results, and Chronic Liver Disease Questionnaire (CLDQ) results. Possible future exploratory efficacy parameters include HDV RNA sequencing for patients with non-response or HDV RNA rebound on therapy.
Safety:
To assess the safety and tolerability of the study drugs, the following will be monitored: adverse events (AEs), clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, physical examinations, ophthalmological assessments, semen analyses (as applicable), electrocardiograms (ECGs), concomitant medications, and depression (as applicable). In addition, to monitor the safety of the anti-HBV nucleotide, tenofovir, bone density will be monitored for some patients.
Inclution Criteria
Inclusion Criteria
1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV antibody (Ab) test and HDV
RNA ≥ 500 IU/mL by quantitative polymerase chain reaction (qPCR) at study entry.
Note: Non-genotype 1 HDV will be capped at 15% of total enrollment. Patients with a screening HDV RNA viral
load ≤ 4 log10 will make up between 35% and 45% of the total population.
2. Demonstrable suppression of HBV DNA (< 20 IU/mL) 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. Willing and able to comply with study procedures and provide written informed consent.
5. Need to be able to read and understand language where the patient is participating in the study.
6. Need to be able to self-administer medication orally and via subcutaneous (SC) injection.
7. Male and female participants who are 18 years of age or above.
8. Body mass index (BMI) of ≥ 18 kg/m2 and weight ≥ 45 kg.
9. Liver biopsy within 45 days of Day 1 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.
10. ECGs demonstrating no acute ischemia or clinically significant (CS) abnormality and a corrected QT interval by Fridericia
correction formula (QTcF) < 450 ms.
11. Normal dilated retinal examination.
12. 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 study. 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:
• Progestogen injection (eg, Depo-Provera®) for ≥ 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
• 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 nonbarrier method
(eg, copper IUD), or a nonhormonal barrier method (eg, diaphragm with spermicide or cervical cap with spermicide).
1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV antibody (Ab) test and HDV
RNA ≥ 500 IU/mL by quantitative polymerase chain reaction (qPCR) at study entry.
Note: Non-genotype 1 HDV will be capped at 15% of total enrollment. Patients with a screening HDV RNA viral
load ≤ 4 log10 will make up between 35% and 45% of the total population.
2. Demonstrable suppression of HBV DNA (< 20 IU/mL) 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. Willing and able to comply with study procedures and provide written informed consent.
5. Need to be able to read and understand language where the patient is participating in the study.
6. Need to be able to self-administer medication orally and via subcutaneous (SC) injection.
7. Male and female participants who are 18 years of age or above.
8. Body mass index (BMI) of ≥ 18 kg/m2 and weight ≥ 45 kg.
9. Liver biopsy within 45 days of Day 1 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.
10. ECGs demonstrating no acute ischemia or clinically significant (CS) abnormality and a corrected QT interval by Fridericia
correction formula (QTcF) < 450 ms.
11. Normal dilated retinal examination.
12. 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 study. 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:
• Progestogen injection (eg, Depo-Provera®) for ≥ 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
• 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 nonbarrier method
(eg, copper IUD), or a nonhormonal barrier method (eg, diaphragm with spermicide or cervical cap with spermicide).
Exclusion Criteria
Exclusion Criteria
General Exclusions
1. Participation in a clinical trial with, or use of, any investigational agent within 30 days or 5 half-lives, whichever
is longer, before screening.
2. Previous use of LNF within 12 months before pre-screening/screening or during the study.
3. 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.
Exclusions Based on Disease
4. Current or previous history of decompensated liver disease (Child-Pugh Class B or C).
• For patients categorized as Child-Pugh A (with a score of 5) with well compensated liver disease, enrollment will be
allowed.
5. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) by detectable HIV RNA and HCV
RNA, respectively.
6. Positive results for HIV or HCV Ab at screening. Patients with a positive HCV Ab at screening are allowed if they have
completed a curative antiviral regimen and have documented undetectable HCV RNA for at least 3 months before screening
and at screening.
7. Evidence of significant portal hypertension such as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg; current
presence or history of esophageal or abdominal varices, variceal bleeding, or splenomegaly > 12 cm length on imaging.
In a case when the spleen measures larger than 12 cm and the Principal Investigator believes the subject meets all other
non-cirrhotic criteria, a discussion with the Medical Monitor is warranted for patient inclusion.
8. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.
9. Any of the following abnormal laboratory test results at screening:
• Platelet count < 90,000 cells/mm3
• White blood cell (WBC) count < 3,000 cells/mm3
• Absolute neutrophil count (ANC) < 1,500 cells/mm3
• Hemoglobin
− < 11 g/dL for women
− < 12 g/dL for men
• Confirmed creatinine clearance (< 30 mL/min by Cockroft-Gault)
• Alpha-fetoprotein ≥ 100 ng/mL
• Abnormal thyroid-stimulating hormone (TSH) or total thyroxine (T4) levels
− Patients with well-controlled thyroid function may be enrolled following discussion with the Medical Monitor.
10. 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).
11. History of hepatocellular carcinoma.
12. Patients with any of the following:
• Current eating disorder (as defined by Diagnostic and Statistical Manual of Mental Disorders [DSM]-5)
• Evidence of alcohol substance use disorder, as defined by DSM-5, or excessive intake, defined as follows:
− > 20 g/day for females (1.5 standard alcohol drinks) or
− > 30 g/day for males (2.0 standard alcohol drinks).
Note: A standard drink contains 14 g of alcohol:
355 mL/12 oz of beer, 148 mL/5 oz of wine, or
44 mL/1.5 oz of spirits.
• Blood alcohol concentration > 0.08%.
Drug abuse within the previous 6 months before screening, with the exception of cannabinoids and their derivatives.
13. Prior history or current evidence of any of the following:
• Immunologically mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, severe psoriasis,
systemic lupus erythematosus) that requires more than intermittent nonsteroidal anti-inflammatory medications for
management or that requires chronic use of systemic corticosteroids in the 6 months before screening (periodic
use of oral steroid taper and inhaled asthma medications are allowed),
• Retinal disorder or clinically relevant ophthalmic disorder,
• Any malignancy within 5 years before screening.
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,
• Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease (including history of angina,
myocardial infarction, or interventional procedure for coronary artery disease),
• Chronic pulmonary disease (eg, chronic obstructive pulmonary disease) associated with functional impairment,
as defined by a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio < 0.7,
• Pancreatitis or colitis,
• Severe or uncontrolled psychiatric disorder (eg, depression, manic condition, psychosis, acute and/or chronic cognitive
dysfunction, suicidal behavior, history of suicide attempt, and relapse of substance abuse),
− Refer to Section 11.3.8 for information regarding depression monitoring.
Bone marrow or solid organ transplantation.
− For patients who are stable for 1 year post-transplantation and do not require immunosuppressive therapy(ies), following a case review, enrollment may be considered.
14. Other significant medical condition that may require intervention during the study. Patients with any serious
condition that, in the opinion of the Medical Monitor, would preclude evaluation of response or make it unlikely that the
contemplated course of therapy and follow-up could be completed. Patients for whom participation in the study would
increase their risk.
15. 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.
Exclusions Based on Concurrent Medication Use
16. Any prescription, over-the-counter (OTC) product, or herbal product that is not approved by the Medical Monitor (refer to
the Concomitant Medication Manual for guidance),
17. Consumption of grapefruit, Seville oranges, or product that contains grapefruit or Seville oranges within 14 days of
Baseline (Day 1).
18. Therapy with an immunomodulatory agent, IFN-α (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 and during the study.
• Periodic use of oral steroids or inhaled steroids to manage asthma is acceptable.
19. Use of heparin or warfarin during the study.
20. Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV within 14 days before study
randomization or have a chronic condition that would likely require such therapy during the study.
21. Long-term treatment (> 2 weeks) before or during the study with agents that have a high risk for nephrotoxicity or
hepatotoxicity unless it is approved by the Medical Monitor.
22. Receipt of systemic immunosuppressive therapy within 3 months before screening or during the study.
23. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir, or other
substances that are part of study treatment.
24. Concomitant use (within 2 weeks of Day 1 and throughout study conduct) of any of the following:
• Medications (prescription, OTC, herbal products) or foods that are known moderate or strong inducers of CYP3A or
sensitive substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, UGT1A1, P-gp,
and OCT1,
• Drugs known to prolong the PR or QT interval unless otherwise described in this protocol,
• Statins (with the exception of pravastatin).
25. Concomitant use of medications contraindicated in the prescribing information for RTV, PEG IFN-alfa-2a, tenofovir,
or entecavir.
Note: Any requests for rescreening following a screening failure need to be discussed with the Principal Investigator and the Medical Monitor.
General Exclusions
1. Participation in a clinical trial with, or use of, any investigational agent within 30 days or 5 half-lives, whichever
is longer, before screening.
2. Previous use of LNF within 12 months before pre-screening/screening or during the study.
3. 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.
Exclusions Based on Disease
4. Current or previous history of decompensated liver disease (Child-Pugh Class B or C).
• For patients categorized as Child-Pugh A (with a score of 5) with well compensated liver disease, enrollment will be
allowed.
5. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) by detectable HIV RNA and HCV
RNA, respectively.
6. Positive results for HIV or HCV Ab at screening. Patients with a positive HCV Ab at screening are allowed if they have
completed a curative antiviral regimen and have documented undetectable HCV RNA for at least 3 months before screening
and at screening.
7. Evidence of significant portal hypertension such as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg; current
presence or history of esophageal or abdominal varices, variceal bleeding, or splenomegaly > 12 cm length on imaging.
In a case when the spleen measures larger than 12 cm and the Principal Investigator believes the subject meets all other
non-cirrhotic criteria, a discussion with the Medical Monitor is warranted for patient inclusion.
8. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.
9. Any of the following abnormal laboratory test results at screening:
• Platelet count < 90,000 cells/mm3
• White blood cell (WBC) count < 3,000 cells/mm3
• Absolute neutrophil count (ANC) < 1,500 cells/mm3
• Hemoglobin
− < 11 g/dL for women
− < 12 g/dL for men
• Confirmed creatinine clearance (< 30 mL/min by Cockroft-Gault)
• Alpha-fetoprotein ≥ 100 ng/mL
• Abnormal thyroid-stimulating hormone (TSH) or total thyroxine (T4) levels
− Patients with well-controlled thyroid function may be enrolled following discussion with the Medical Monitor.
10. 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).
11. History of hepatocellular carcinoma.
12. Patients with any of the following:
• Current eating disorder (as defined by Diagnostic and Statistical Manual of Mental Disorders [DSM]-5)
• Evidence of alcohol substance use disorder, as defined by DSM-5, or excessive intake, defined as follows:
− > 20 g/day for females (1.5 standard alcohol drinks) or
− > 30 g/day for males (2.0 standard alcohol drinks).
Note: A standard drink contains 14 g of alcohol:
355 mL/12 oz of beer, 148 mL/5 oz of wine, or
44 mL/1.5 oz of spirits.
• Blood alcohol concentration > 0.08%.
Drug abuse within the previous 6 months before screening, with the exception of cannabinoids and their derivatives.
13. Prior history or current evidence of any of the following:
• Immunologically mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, severe psoriasis,
systemic lupus erythematosus) that requires more than intermittent nonsteroidal anti-inflammatory medications for
management or that requires chronic use of systemic corticosteroids in the 6 months before screening (periodic
use of oral steroid taper and inhaled asthma medications are allowed),
• Retinal disorder or clinically relevant ophthalmic disorder,
• Any malignancy within 5 years before screening.
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,
• Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease (including history of angina,
myocardial infarction, or interventional procedure for coronary artery disease),
• Chronic pulmonary disease (eg, chronic obstructive pulmonary disease) associated with functional impairment,
as defined by a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio < 0.7,
• Pancreatitis or colitis,
• Severe or uncontrolled psychiatric disorder (eg, depression, manic condition, psychosis, acute and/or chronic cognitive
dysfunction, suicidal behavior, history of suicide attempt, and relapse of substance abuse),
− Refer to Section 11.3.8 for information regarding depression monitoring.
Bone marrow or solid organ transplantation.
− For patients who are stable for 1 year post-transplantation and do not require immunosuppressive therapy(ies), following a case review, enrollment may be considered.
14. Other significant medical condition that may require intervention during the study. Patients with any serious
condition that, in the opinion of the Medical Monitor, would preclude evaluation of response or make it unlikely that the
contemplated course of therapy and follow-up could be completed. Patients for whom participation in the study would
increase their risk.
15. 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.
Exclusions Based on Concurrent Medication Use
16. Any prescription, over-the-counter (OTC) product, or herbal product that is not approved by the Medical Monitor (refer to
the Concomitant Medication Manual for guidance),
17. Consumption of grapefruit, Seville oranges, or product that contains grapefruit or Seville oranges within 14 days of
Baseline (Day 1).
18. Therapy with an immunomodulatory agent, IFN-α (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 and during the study.
• Periodic use of oral steroids or inhaled steroids to manage asthma is acceptable.
19. Use of heparin or warfarin during the study.
20. Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV within 14 days before study
randomization or have a chronic condition that would likely require such therapy during the study.
21. Long-term treatment (> 2 weeks) before or during the study with agents that have a high risk for nephrotoxicity or
hepatotoxicity unless it is approved by the Medical Monitor.
22. Receipt of systemic immunosuppressive therapy within 3 months before screening or during the study.
23. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir, or other
substances that are part of study treatment.
24. Concomitant use (within 2 weeks of Day 1 and throughout study conduct) of any of the following:
• Medications (prescription, OTC, herbal products) or foods that are known moderate or strong inducers of CYP3A or
sensitive substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, UGT1A1, P-gp,
and OCT1,
• Drugs known to prolong the PR or QT interval unless otherwise described in this protocol,
• Statins (with the exception of pravastatin).
25. Concomitant use of medications contraindicated in the prescribing information for RTV, PEG IFN-alfa-2a, tenofovir,
or entecavir.
Note: Any requests for rescreening following a screening failure need to be discussed with the Principal Investigator and the Medical Monitor.
The Estimated Number of Participants
-
Taiwan
35 participants
-
Global
400 participants
