Chronic Hepatitis b
Conditions
Keywords
Hepatitis B virus, Chronic hepatitis B, HBV, Hepatitis, CHB
Brief summary
This is a randomized, open label, multicenter Phase 2 study investigating the safety and antiviral activity of AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNα-2a in subjects with CHB.
Interventions
DRUGAB-729
subcutaneous injection
DRUGPeg-IFNα-2a
subcutaneous injection
Sponsors
Arbutus Biopharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis B virus infection with documentation at least 6 months prior to screening * Subjects must have been receiving either TAF, TDF (or equivalent), or ETV consistently for ≥12 months prior to dosing Day 1 * HBV DNA \<LLOQ at Screening * HBsAg between 100 and 5,000 IU/mL at Screening * Subjects must be HBeAg-negative at Screening * Fibroscan® result of ≤8.5 kPa within 6 months prior to dosing Day 1 * Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
Exclusion criteria
* Evidence of co-infection with hepatitis A, C, D or E virus or human immunodeficiency virus (HIV) at screening * History of any clinically significant medical condition associated with chronic liver disease, cirrhosis, evidence of decompensated liver disease, or findings suggestive of hepatocellular carcinoma (HCC) at any time * Contraindications to the use of Peg-IFNα-2a or incapable of self-administration or assisted administration of Peg-IFNα-2a * Previous treatment with an experimental HBV-directed RNA-interference or antisense oligonucleotide product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Frequency and Severity of Treatment Emergent Adverse Events (TEAEs), Discontinuations Due to AEs and Lab Abnormalities After Dosing With AB-729 Plus Peg-IFNα-2a | Up to 124 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in HBsAg and Other Virologic Markers at Each Time Point | Up to 124 weeks |
| Proportion of Subjects With HBsAb Seroconversion at Each Timepoint | Up to 124 weeks |
| Proportion of Subjects Who Are Eligible to Stop NA After Week 24 of Follow up | Up to 76 weeks |
| Proportion of Subjects Who Discontinue NA and Subsequently Restart NA Therapy After Meeting Criteria | Up to 124 weeks |
| Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Clinical Relapse Criteria. Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Viral Relapse Criteria | Up to 124 weeks |
| Post-dose Plasma Concentrations of AB-729 Anti-sense (AS), AB-729 AS(N-1)3', and AB-729 AS(N-2)3' at Selected Timepoints | Up to 40 weeks |
Countries
Australia, Hong Kong, Moldova, South Korea, Taiwan, Ukraine, United States
Participant flow
Recruitment details
A total of 43 virally suppressed, HBeAg-negative CHB subjects were randomized across 4 cohorts (Cohort A1, N = 12; Cohort A2, N = 13; Cohort B1, N = 8; Cohort B2, N = 10).
Pre-assignment details
24 week lead-in period of imdusiran 60 mg SC every 8 weeks (Q8W) x4 doses added to ongoing SOC NA therapy
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.2 Years |
| Background Nucleos(t)ide Analog Entecavir | 2 Participants |
| Background Nucleos(t)ide Analog Tenofovir alafenamide | 5 Participants |
| Background Nucleos(t)ide Analog Tenofovir disoproxil fumarate | 2 Participants |
| Baseline ALT (U/L) | 30.0 U/L STANDARD_DEVIATION 13.24 |
| Baseline HBsAg (Log10 IU/mL) | 2.944 Log10 IU/mL STANDARD_DEVIATION 0.3361 |
| Baseline HBV DNA (IU/mL) | 1.0 IU/mL STANDARD_DEVIATION 0 |
| Body Mass Index (kg/m2) | 25.79 kg/m2 STANDARD_DEVIATION 6.513 |
| Height (cm) | 170.78 cm STANDARD_DEVIATION 6.164 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 12 Participants |
| Race/Ethnicity, Customized Not Reported/Unknown | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
| Weight (kg) | 75.40 kg STANDARD_DEVIATION 23.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 12 | 0 / 13 | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 23 / 43 | 11 / 12 | 11 / 13 | 8 / 8 | 9 / 10 |
| serious Total, serious adverse events | 0 / 43 | 1 / 12 | 0 / 13 | 0 / 8 | 1 / 10 |
Outcome results
None listed