Clinical Trials List
Protocol NumberARB-001467-003
2018-01-01 - 2020-12-31
Phase II
Terminated4
ICD-10B18.1
Chronic viral hepatitis B without delta-agent
ICD-10B18
Chronic viral hepatitis
ICD-9070.32
Viral hepatitis B without mention of hepatic coma, chronic, without mention of hepatitis delta
A Phase 2a, Open-Label, Study Evaluating the Safety and Anti-Viral Activity of ARB-001467 in Non-Cirrhotic, HBeAg-Negative Subjects with Chronic HBV Infection (Genotype A or B) in Combination with PEG-IFN α-2a and Tenofovir Disoproxil Fumarate
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Arbutus Biopharma Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 余健鈞 Digestive System Department
- Shih-Jer Hsu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Hung-Wei Wang Digestive System Department
- Hung-Yao Chen Digestive System Department
- 陳昇弘 Digestive System Department
- 蘇文邦 Digestive System Department
- Wei-Fan Hsu Digestive System Department
- Hsueh-Chou Lai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
林俊彥
Co-Principal Investigator
- Chien-Hao Huang Digestive System Department
- I-Shyan Sheen Digestive System Department
- Wen-Juei Jeng Digestive System Department
- Yi-Cheng Chen Digestive System Department
- 滕威 Digestive System Department
- 陳威廷 Digestive System Department
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Jee-Fu Huang Digestive System Department
- Chia-Yen Dai Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Chung-Feng Huang Digestive System Department
- Wan-Long Chuang Digestive System Department
- 黃駿逸 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Chronic HBV Infection (Genotype A or B)
Objectives
To explore the anti-viral efficacy of combination therapy with ARB-001467 plus TDF and PEG-IFN α-2a in subjects with chronic hepatitis B (CHB) due to HBV genotype A or B, who are HBV-DNA positive.
Test Drug
ARB-001467 Injection (2 mg/mL)
Active Ingredient
ARB-001467
Dosage Form
Injection
Dosage
2
Endpoints
1. Efficacy:
Proportion of treated subjects with HBsAg decline ≥2 log10 at Week 30
2. Safety:On-treatment safety as measured by frequency of AEs, discontinuations due to
AEs, and selected Grade 3-4 laboratory abnormalities (including hematologic and
liver function, based on CTCAE criteria)
3. Pharmacokinetics: NA
4. Quality of life: NA
Proportion of treated subjects with HBsAg decline ≥2 log10 at Week 30
2. Safety:On-treatment safety as measured by frequency of AEs, discontinuations due to
AEs, and selected Grade 3-4 laboratory abnormalities (including hematologic and
liver function, based on CTCAE criteria)
3. Pharmacokinetics: NA
4. Quality of life: NA
Inclution Criteria
Main inclusion criteria:
1. Adult subjects, 18 (or other appropriate age of consent) to 65 years of age, inclusive
2. Body mass index (BMI) ≥18 kg/m2
and ≤35 kg/m2
3. Chronic HBV infection as documented at screening by either:
a. Positive HBsAg, or hepatitis B virus e-antigen (HBeAg; negative or positive) or
HBV-DNA at least 6 months prior to screening; OR
b. Historical liver biopsy consistent with chronic HBV infection with documentation
available at screening
4. Subject must be HBV-DNA(+) with a HBV-DNA ≥1000 IU/mL and either treatmentnaïve or treatment-experienced, defined as follows:
a. Treatment naïve subjects: Subjects have never received nucleos(t)ide analogue (NA)
therapies including, but not limited to, TDF, entecavir, telbivudine, or lamivudine
and/or interferon-alfa; OR
b. Treatment experienced subjects: Subjects may have previously had NA therapies
(including, but not limited to, TDF, entecavir, telbivudine, or lamivudine) and/or
interferon-alfa therapy, but must have discontinued treatment at least 6 months prior to screening
5. Quantitative HBsAg ≥1000 IU/mL and ≤10000 IU/mL at the Screening Visit
6. HBV genotype A or B at the screening visit
7. Interleukin (IL)28B CC Genotype
8. HBeAg-negative at the screening visit
9. All subjects must have assessment of fibrosis demonstrating non-cirrhotic status available
at screening. Non-cirrhotic subjects are defined by:
a. Liver biopsy demonstrating a Metavir Fibrosis Score of F0-3 (or equivalent) ≤6 months prior to Day 1 OR
b. Fibroscan® result of ≤10 kPa. Note: a confirmatory Fibroscan® is required ≤6 months prior to Day 1
10. Liver ultrasound with absence of clinically significant abnormalities is required ≤6 months prior to Day°1
11. Ability to review and agree to the nature of the study and sign the informed consent
document and comply with all protocol-specified visit schedules and requirements
12. Male subjects must agree to use contraception as defined in Appendix 5: Contraceptive
Guidance and Collection of Pregnancy Information, starting 2 weeks prior to the first dose
of study drug, during the treatment period, and for at least 2 weeks plus 90 days (duration
of spermatogenesis) for a total of 104 days after the last dose of study treatment, and
refrain from donating sperm during this period
13. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at
least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 5:
Contraceptive Guidance and Collection of Pregnancy Information; OR
b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5:
Contraceptive Guidance and Collection of Pregnancy Information, starting 2 weeks
prior to the first dose of study drug, during the treatment period, and for at least 2
weeks plus 30 days (duration of ovulatory cycle) for a total of 44 days after the last dose of study treatment
1. Adult subjects, 18 (or other appropriate age of consent) to 65 years of age, inclusive
2. Body mass index (BMI) ≥18 kg/m2
and ≤35 kg/m2
3. Chronic HBV infection as documented at screening by either:
a. Positive HBsAg, or hepatitis B virus e-antigen (HBeAg; negative or positive) or
HBV-DNA at least 6 months prior to screening; OR
b. Historical liver biopsy consistent with chronic HBV infection with documentation
available at screening
4. Subject must be HBV-DNA(+) with a HBV-DNA ≥1000 IU/mL and either treatmentnaïve or treatment-experienced, defined as follows:
a. Treatment naïve subjects: Subjects have never received nucleos(t)ide analogue (NA)
therapies including, but not limited to, TDF, entecavir, telbivudine, or lamivudine
and/or interferon-alfa; OR
b. Treatment experienced subjects: Subjects may have previously had NA therapies
(including, but not limited to, TDF, entecavir, telbivudine, or lamivudine) and/or
interferon-alfa therapy, but must have discontinued treatment at least 6 months prior to screening
5. Quantitative HBsAg ≥1000 IU/mL and ≤10000 IU/mL at the Screening Visit
6. HBV genotype A or B at the screening visit
7. Interleukin (IL)28B CC Genotype
8. HBeAg-negative at the screening visit
9. All subjects must have assessment of fibrosis demonstrating non-cirrhotic status available
at screening. Non-cirrhotic subjects are defined by:
a. Liver biopsy demonstrating a Metavir Fibrosis Score of F0-3 (or equivalent) ≤6 months prior to Day 1 OR
b. Fibroscan® result of ≤10 kPa. Note: a confirmatory Fibroscan® is required ≤6 months prior to Day 1
10. Liver ultrasound with absence of clinically significant abnormalities is required ≤6 months prior to Day°1
11. Ability to review and agree to the nature of the study and sign the informed consent
document and comply with all protocol-specified visit schedules and requirements
12. Male subjects must agree to use contraception as defined in Appendix 5: Contraceptive
Guidance and Collection of Pregnancy Information, starting 2 weeks prior to the first dose
of study drug, during the treatment period, and for at least 2 weeks plus 90 days (duration
of spermatogenesis) for a total of 104 days after the last dose of study treatment, and
refrain from donating sperm during this period
13. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at
least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 5:
Contraceptive Guidance and Collection of Pregnancy Information; OR
b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5:
Contraceptive Guidance and Collection of Pregnancy Information, starting 2 weeks
prior to the first dose of study drug, during the treatment period, and for at least 2
weeks plus 30 days (duration of ovulatory cycle) for a total of 44 days after the last dose of study treatment
Exclusion Criteria
1. Known co-infection with any of the following:
a. Human immunodeficiency virus (HIV),
b. Hepatitis C virus (HCV),
c. Hepatitis D virus (HDV),
d. Hepatitis E virus (HEV).
2. Treatment with any investigational drug or enrollment in any other clinical study ≤3
months prior to the first dose of study treatment, or at any time during participation in the
study; or collection of additional blood, urine, or tissue samples beyond those specified in
this study or required as part of the subject’s medical care
3. Receiving or planning to receive systemic immunosuppressive medications during the
study or ≤2 months prior to the first dose of study treatment, including but not limited to:
prednisone (>10 mg/day), methotrexate, or cyclosporine
4. Receiving or planning to receive any medications known to cause acute renal insufficiency
(e.g., aminogylcosides, vancomycin, etc.)
5. Significant immunosuppression from, but not limited to, immunodeficiency conditions
such as common variable hypogammaglobulinemia
6. Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior
to the Screening Visit, except for those subjects monitored in an opioid substitution
maintenance program
7. Any known pre-existing medical or psychiatric condition that could interfere with the
subject’s ability to provide informed consent or participate in study conduct, or that may
confound study findings including, but not limited to:
a. History of clinically significant medical condition associated with other chronic liver
disease (e.g., Hemochromatosis, autoimmune hepatitis, Wilson’s disease,
α-1-antitrypsin deficiency, alcoholic liver disease, non-alcoholic steatohepatitis, or
toxin exposures) that may affect the ability to respond to HBV therapy
b. Immunologically-mediated disease e.g., inflammatory bowel disease (Crohn’s disease,
ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic
lupus erythematosus, scleroderma, or sarcoidosis
c. Current or history of any clinically significant cardiac abnormalities/dysfunction e.g.,
congestive heart failure, myocardial infarction ≤6 months prior to the Screening Visit,
pulmonary hypertension, complex congenital heart disease, significant arrhythmia,
active cardiac ischemia
d. Current uncontrolled hypertension or past medical history of hypertensive crisis.
e. Evidence of decompensated liver disease including, but not limited to, a history or
presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, or
hepatic encephalopathy
f. Liver ultrasound or other imaging with findings suggestive of hepatocellular carcinoma
(HCC)
g. Clinically unstable medical condition ≤1 week prior to the first dose of study treatment
h. Psychiatric condition(s), including but not limited to suicidal or homicidal ideation and/or attempt
8. Poor venous access that precludes routine peripheral blood sampling or IV infusion required for this study
9. Evidence of active or suspected malignancy, or a history of malignancy ≤3 years prior to
the Screening Visit (except adequately treated carcinoma in situ and basal cell carcinoma
of the skin). Subjects under evaluation for malignancy are not eligible
10. Known or suspected hypersensitivity or previous severe reactions to any of the
constituents of ARB-001467, other lipid-based products, products containing polyethylene
glycol, TDF, interferon (IFN), or the drugs used in the pre-treatment regimen
(dexamethasone, ibuprofen, H1 and H2 blockers)
11. Any contraindication to IFN or TDF or the components of either, per the approved package inserts
12. Pregnant or nursing, or who intend to become pregnant during the study
13. Male subjects with partners who are, or intend to become, pregnant during the study
14. Employed as site personnel directly involved with this study
15. History of life-threatening serious adverse event (SAE) during the Screening period
16. Any previous treatment with an experimental drug for HBV
17. Any subject who previously discontinued or required dose reduction for PEG-IFN α-2a and/or TDF due to adverse events
a. Human immunodeficiency virus (HIV),
b. Hepatitis C virus (HCV),
c. Hepatitis D virus (HDV),
d. Hepatitis E virus (HEV).
2. Treatment with any investigational drug or enrollment in any other clinical study ≤3
months prior to the first dose of study treatment, or at any time during participation in the
study; or collection of additional blood, urine, or tissue samples beyond those specified in
this study or required as part of the subject’s medical care
3. Receiving or planning to receive systemic immunosuppressive medications during the
study or ≤2 months prior to the first dose of study treatment, including but not limited to:
prednisone (>10 mg/day), methotrexate, or cyclosporine
4. Receiving or planning to receive any medications known to cause acute renal insufficiency
(e.g., aminogylcosides, vancomycin, etc.)
5. Significant immunosuppression from, but not limited to, immunodeficiency conditions
such as common variable hypogammaglobulinemia
6. Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior
to the Screening Visit, except for those subjects monitored in an opioid substitution
maintenance program
7. Any known pre-existing medical or psychiatric condition that could interfere with the
subject’s ability to provide informed consent or participate in study conduct, or that may
confound study findings including, but not limited to:
a. History of clinically significant medical condition associated with other chronic liver
disease (e.g., Hemochromatosis, autoimmune hepatitis, Wilson’s disease,
α-1-antitrypsin deficiency, alcoholic liver disease, non-alcoholic steatohepatitis, or
toxin exposures) that may affect the ability to respond to HBV therapy
b. Immunologically-mediated disease e.g., inflammatory bowel disease (Crohn’s disease,
ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic
lupus erythematosus, scleroderma, or sarcoidosis
c. Current or history of any clinically significant cardiac abnormalities/dysfunction e.g.,
congestive heart failure, myocardial infarction ≤6 months prior to the Screening Visit,
pulmonary hypertension, complex congenital heart disease, significant arrhythmia,
active cardiac ischemia
d. Current uncontrolled hypertension or past medical history of hypertensive crisis.
e. Evidence of decompensated liver disease including, but not limited to, a history or
presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, or
hepatic encephalopathy
f. Liver ultrasound or other imaging with findings suggestive of hepatocellular carcinoma
(HCC)
g. Clinically unstable medical condition ≤1 week prior to the first dose of study treatment
h. Psychiatric condition(s), including but not limited to suicidal or homicidal ideation and/or attempt
8. Poor venous access that precludes routine peripheral blood sampling or IV infusion required for this study
9. Evidence of active or suspected malignancy, or a history of malignancy ≤3 years prior to
the Screening Visit (except adequately treated carcinoma in situ and basal cell carcinoma
of the skin). Subjects under evaluation for malignancy are not eligible
10. Known or suspected hypersensitivity or previous severe reactions to any of the
constituents of ARB-001467, other lipid-based products, products containing polyethylene
glycol, TDF, interferon (IFN), or the drugs used in the pre-treatment regimen
(dexamethasone, ibuprofen, H1 and H2 blockers)
11. Any contraindication to IFN or TDF or the components of either, per the approved package inserts
12. Pregnant or nursing, or who intend to become pregnant during the study
13. Male subjects with partners who are, or intend to become, pregnant during the study
14. Employed as site personnel directly involved with this study
15. History of life-threatening serious adverse event (SAE) during the Screening period
16. Any previous treatment with an experimental drug for HBV
17. Any subject who previously discontinued or required dose reduction for PEG-IFN α-2a and/or TDF due to adverse events
The Estimated Number of Participants
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Taiwan
15 participants
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Global
30 participants
