Hepatitis B virus e-antigen (HBeAg)-negative and HBeAg-positive subjects with chronic Hepatitis B virus (HBV) MedDRA version: 20.0 Level: LLT Classification code 10054283 Term: HBV DNA detectable System Organ Class: 100000004848
Conditions
Interventions
Product Name: ARB-001467
Product Code: ARB-001467
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not assigned
Current Sponsor code: UsiHBV-1 (composed of three RNA duplexes: G9-8, P6-
Sponsors
Arbutus Biopharma Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Documented chronic HBV infection for =12 months prior to Screening Visit. 2. Quantitative HBV surface antigen (HBsAg) =1000 IU/mL by Elecsys HBsAg II (Roche) or Architect HBsAg QT (Abbott) at the Screening Visit. Subjects with HBsAg levels 3 months prior to the Screening Visit available for review. 5. All subjects must have a Fibroscan® result of =9 kPa at the Screening assessment. 6. Adult subjects, 18 (or other appropriate age of consent) to 70 years of age, inclusive. 7. Body mass index (BMI) =18 kg/m2 and =35 kg/m2. 8. 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. 9. Female subjects of child-bearing potential must not be pregnant or lactating, must have a negative pregnancy test at Screening and must be practicing an adequate method of birth control. Male subjects with female partners of child-bearing potential must also practice an adequate method of birth control. Refer to the protocol for additional details. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
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); OR 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 interferon during the study or =12 months prior to the first dose of study treatment. 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. Immunologically-mediated disease e.g., inflammatory bowel disease (Crohn’s disease, ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, scleroderma, or sarcoidosis. b. 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. c. Current uncontrolled hypertension or past medical history of hypertensive crisis. d. 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. e. Clinically unstable medical condition =1 week prior to the first dose of study treatment. f. 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 intravenous (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, or products containing polyethylene glycol or the drugs used in the pre-treatment regimen (dexamethasone, ibuprofen, H1 and H2 blockers). 11. Pregnant or nursing, or who intend to become pregnant during the study. 12. Male subjects with partners who are, or intend to become, pregnant during the study. 13. Employed as site personnel directly involved with this study. 14. History of life-threatening SAE during the Screening period. Laboratory Exclusion Criteria If any of the following laboratory exclusion criteria are met, then the site may have t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of multiple doses of ARB-001467 in Hepatitis B virus e-antigen (HBeAg)-negative and HBeAg-positive subjects with chronic Hepatitis B virus (HBV) infection who are receiving nucleos(t)ide analogue (NA) therapy.;Secondary Objective: Secondary - To evaluate the pharmacokinetics (PK) of multiple doses of ARB-001467 in subjects with CHB. - To evaluate antiviral activity of ARB-001467 for up to 72 weeks after the first dose of study treatment. Exploratory - To describe drug-resistant HBV variants associated with virologic breakthrough. - To explore the relationship between anti-viral activity and exposure to ARB-001467. - To explore the relationship between immunological markers and exposure to ARB-001467.;Primary end point(s): The frequency and severity of treatment-emergent serious adverse events (SAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities, by cohort.;Timepoint(s) of evaluation of this end point: Throughout the trial and until 28 days after the last infusion of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary - ARB-001467 PK at multiple time points from baseline through Day 85 (i.e., 28 days after the last infusion of study treatment) in cohorts 1 to 3 and cohort 4 (without extended treatment) and from baseline through 36 weeks of treatment (cohort 4 extended treatment). - The proportion of subjects in each dose level cohort with =0.5 log10 HBsAg decrease from baseline at EOS, and for these subjects, the changes from baseline (expressed as percentage and log10 change) in the following virologic markers will be assessed throughout the study: - Quantitative HBV surface antigen (HBsAg) - Quantitative HBV surface antibody (HBsAb) - Quantitative HBV-DNA and HBV-RNA (viral load) For the HBeAg-positive cohort only: - Quantitative HBV e-antigen (HBeAg) Exploratory - Identification of drug resistance mutations from RNA sequencing of drug-resistant HBV variants. - Assessment of the relationships between PK and virologic markers. - Assessment of the relationships between PK and immunologic markers.;Timepoint(s) of evaluation of this end point: ARB-001467 PK at multiple time points from baseline through Day 85 (i.e., 28 days after the last infusion of study treatment) in cohorts 1 to 3 and cohort 4 without extended treatment) and from baseline through 36 weeks of treatment (cohort 4 extended treatment). The proportion of subjects in each dose level cohort with changes from baseline will be assessed throughout the study. | — |
Countries
Australia, New Zealand, Romania, United Kingdom
Contacts
Public ContactArbutus Regulatory Affairs
Arbutus Biopharma Corporation
Outcome results
None listed