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Trial registered on ANZCTR


Registration number
ACTRN12619001197123
Ethics application status
Approved
Date submitted
31/07/2019
Date registered
27/08/2019
Date last updated
27/08/2019
Date data sharing statement initially provided
27/08/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AB-729 Administered by Subcutaneous Injection to Subjects with Chronic Hepatitis B Infection
Scientific title
Part 2 of a three part study-- A Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AB-729 Administered by Subcutaneous Injection to Subjects with Chronic Hepatitis B Infection
Secondary ID [1] 298572 0
AB-729-001
Universal Trial Number (UTN)
U1111-1227-7086
Trial acronym
Linked study record
ACTRNs number: ACTRN12619000954123
It is the second part of the study as in this study there are 3 parts.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Infection (CHB) 313411 0
Condition category
Condition code
Infection 311845 311845 0 0
Other infectious diseases
Oral and Gastrointestinal 311846 311846 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in 3 parts. Part 2 will be an open-label, SAD design and will be conducted in 24 subjects with CHB infection.
Part 2: This part will be approximately 12 weeks. Approximately 24 non-cirrhotic subjects with CHB infection will enroll in Part 2 in up to 4 cohorts (Cohorts A, B, C, and D).
The starting dose of AB-729 administered to Cohort A will be approved by the Investigator and Sponsor Medical Monitor based on safety and tolerability data from the two initial single doses in healthy subjects in Part 1 and will not exceed the maximum dose found to be safe and tolerable. Doses in subsequent cohorts will not exceed those tested in Part 1 and are subject to approval of the Investigator, Sponsor Medical Monitor, and an independent external safety reviewer with expertise in HBV.
All doses of AB-729 will be administered at the study site by study staff members. Each participant will receive a single dose of AB-729 only.
Frequency/duration of each dose: Single dose study for Part 2

mode of administration: Subcutaneous injection
Intervention code [1] 314832 0
Treatment: Drugs
Comparator / control treatment
Not Applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320517 0
To evaluate the safety and tolerability of AB-729 following administration by SC injection of single doses to subjects with CHB infection as assessed by the frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities.

Examples of known/possible adverse reactions/events:
This is a first in human study, so we have no known adverse events to disclose. Based on similar compounds in different early clinical trials, there may be a low incidence of mild redness, bruising or pain at the injection site. This will be assessed by clinical site staff during clinic visits and by participant diaries.
Timepoint [1] 320517 0
Monitored during screening, Day 1, Day 3, Day 8, Day 15, Day 22, Day 29 and Post-Treatment Follow-up visits at 8 and 12 weeks post-dose.
Secondary outcome [1] 371893 0
To evaluate changes in concentration of HBsAg in subjects with CHB infection after single doses of AB-729 assessed by change from baseline in HBsAg.
Outcome Assessment: Serum assay tests will be used.
Timepoint [1] 371893 0
HBsAg will be performed throughout study
Screening, Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Week 8, Week 12
Secondary outcome [2] 371894 0
To characterize the single dose PK of AB-729 in subjects with CHB, e.g., maximum concentration [Cmax]), time to Cmax (Tmax), area under the concentration-time curve from time of dosing to the last measurable concentration [AUC(0-t)] and AUC(0-infinity)).
Timepoint [2] 371894 0
Plasma PK samples will be collected in the following timepoints:
Predose (within 60 minutes prior to dosing), 0.25 hours, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours, 24 hours (Day 2), after 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 96 hours (Day 5), Day 8, Day 15, Day 22 and Day 29.
Secondary outcome [3] 371896 0
To evaluate changes in concentration of HBV-RNA in subjects with CHB infection after single doses of AB-729 assessed by change from baseline.
Outcome assessment: Serum assay tests will be used.
Timepoint [3] 371896 0
Quantitative HBV-RNA test will be performed on Day 1, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [4] 371897 0
To evaluate changes in concentration of hepatitis B virus surface antibody in subjects with CHB infection after single doses of AB-729 assessed by change from baseline.
Outcome assessment: Serum assay tests will be used.
Timepoint [4] 371897 0
Quantitative HBsAb test will be performed on Day 1, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [5] 371898 0
To evaluate changes in concentration of Hepatitis B virus e antigen in subjects with CHB infection after single doses of AB-729 assessed by change from baseline.
Outcome assessment: Serum assay tests will be used.
Timepoint [5] 371898 0
Quantitative HBeAg test will be performed on Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [6] 371899 0
To evaluate changes in concentration of Hepatitis B virus e antibody in subjects with CHB infection after single doses of AB-729 assessed by change from baseline.
Outcome assessment: Serum assay tests will be used.
Timepoint [6] 371899 0
Qualitative HBeAb test will be performed on Day 1, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [7] 371900 0
Proportion of subjects with a change in HBsAg from baseline meeting response criteria (greater than or
equal to 0.5, 1, 2, or 3 log10 reduction; less than or equal to lower limit of quantitation [LLOQ]).
Outcome assessment: Serum assay tests will be used.
Timepoint [7] 371900 0
Quantitative HBsAg test will be performed at screening and Day 1, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [8] 371901 0
Proportion of subjects with a change in HBV-DNA from baseline meeting response criteria (greater than or equal to 0.5, 1, 2, or 3 log10 reduction; less than or equal to LLOQ.
Outcome assessment: Serum assay tests will be used.
Timepoint [8] 371901 0
Quantitative HBV-DNA test will be performed at screening, Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [9] 373164 0
To evaluate changes in concentration of HBV-DNA in subjects with CHB infection after single doses of AB-729 assessed by change from baseline in HBV-DNA.
Timepoint [9] 373164 0
Serum assay tests will be used.
Quantitative HBV-DNA test will be performed at screening, Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, week 8 and week 12
Secondary outcome [10] 374049 0
To evaluate changes in concentration of hepatitis B virus core-related antigen in subjects with CHB infection after single doses of AB-729 assessed by change from baseline.
Outcome assessment: Serum assay tests will be used.
Timepoint [10] 374049 0
Quantitative HBcrAg test will be performed on Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, week 8 and week 12

Eligibility
Key inclusion criteria
Inclusion Criteria for Study Part 2:
- Male subjects must agree to use contraception as detailed in the protocol.
- Female subjects must not be pregnant and must agree to use contraception as detailed in the protocol.
- BMI greater than or equal to 18 kg/m2 and lesser than or equal to 38 kg/m2.
- Documented chronic HBV infection as defined in the protocol
- HBV-DNA at screening: For HBV-DNA+ subjects (Cohorts D) only: HBV-DNA greater than or equal to 1,000 IU/mL at Screening. For HBV-DNA- subjects (Cohorts A, B and C) only: HBV-DNA must be lower than the limit of quantitation at Screening.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Study Part 2:
Known co-infection with any of the following:
a. HIV,
b. acute hepatitis A virus (HAV),
c. HCV,
d. hepatitis D virus (HDV), OR
e. hepatitis E virus (HEV) infection.
Any known preexisting 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 any clinically significant medical condition associated with chronic liver disease (e.g.,
hemochromatosis, autoimmune hepatitis, Wilson’s disease, a-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 or significant immunosuppresion
d. Current or history of any clinically significant cardiac abnormalities/dysfunction or uncontrolled
hypertension.
e. Evidence of decompensated liver disease or findings suggestive of HCC at any time.
Evidence of active or suspected malignancy, or a history of malignancy
Findings/Diagnostic Assessments at Screening, confirmed by repeat testing:
- ALT or AST >5 × upper limit of normal (ULN).
- Total bilirubin >1.5 × ULN.
- Alpha fetoprotein (AFP) >100 ng/mL.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14072 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 14073 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 14171 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 26862 0
3168 - Clayton
Recruitment postcode(s) [2] 26863 0
2050 - Camperdown
Recruitment postcode(s) [3] 27124 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 21632 0
Korea, Republic Of
State/province [1] 21632 0
Country [2] 21633 0
Thailand
State/province [2] 21633 0
Country [3] 21634 0
New Zealand
State/province [3] 21634 0
Country [4] 21635 0
Hong Kong
State/province [4] 21635 0
Country [5] 21636 0
Moldova, Republic Of
State/province [5] 21636 0

Funding & Sponsors
Funding source category [1] 303110 0
Commercial sector/Industry
Name [1] 303110 0
Arbutus Biopharma Corporation
Address [1] 303110 0
100 – 8900 Glenlyon Parkway
Burnaby, British Columbia
Canada V5J 5J8
Country [1] 303110 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Arbutus Biopharma Corporation
Address
100 – 8900 Glenlyon Parkway
Burnaby, British Columbia
Canada V5J 5J8
Country
Canada
Secondary sponsor category [1] 303104 0
None
Name [1] 303104 0
Address [1] 303104 0
Country [1] 303104 0
Other collaborator category [1] 280809 0
Commercial sector/Industry
Name [1] 280809 0
Novotech (Australia) Pty Limited
Address [1] 280809 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280809 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303662 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 303662 0
Ministry of Health, Level 3,Rangitoto Room, Unisys Building, 650 Great South Road, Penrose, Auckland
Ethics committee country [1] 303662 0
New Zealand
Date submitted for ethics approval [1] 303662 0
20/03/2019
Approval date [1] 303662 0
06/05/2019
Ethics approval number [1] 303662 0
19/NTB/45
Ethics committee name [2] 303663 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [2] 303663 0
PO Box 2900, 41 Victoria Parade, Fitzroy VIC 3065
Ethics committee country [2] 303663 0
Australia
Date submitted for ethics approval [2] 303663 0
02/04/2019
Approval date [2] 303663 0
30/05/2019
Ethics approval number [2] 303663 0
HREC 060/19

Summary
Brief summary
The study drug AB-729 is being developed as a potential new treatment for Chronic Hepatitis B (CHB). The main goal of the study is to determine whether AB-729 is safe and well tolerated when given at different doses. We will also measure the levels of the drug in the blood at different times.
The study will be conducted in 3 parts. Part 2 will be an open-label, non-randomized, SAD design and will be conducted in 24 subjects with CHB infection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94418 0
Prof Edward Gane
Address 94418 0
Auckland Clinical Studies Ltd and Auckland City Hospital, PO Box 8963, Symonds St, Auckland, 1150
Country 94418 0
New Zealand
Phone 94418 0
+64 21548371
Fax 94418 0
Email 94418 0
EdGane@adhb.govt.nz
Contact person for public queries
Name 94419 0
Mr Michael Child
Address 94419 0
Arbutus Biopharma Corporation,
701 Veterans Circle
Warminster, Pennsylvania
United States , 18974
Country 94419 0
United States of America
Phone 94419 0
+1 267 469 0914
Fax 94419 0
Email 94419 0
clinicaltrials@arbutusbio.com
Contact person for scientific queries
Name 94420 0
Mr Michael Child
Address 94420 0
Arbutus Biopharma Corporation,
701 Veterans Circle
Warminster, Pennsylvania
United States , 18974
Country 94420 0
United States of America
Phone 94420 0
+1 267 469 0914
Fax 94420 0
Email 94420 0
clinicaltrials@arbutusbio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not Applicable
What supporting documents are/will be available?
No other documents available
Summary results
No Results