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Trial registered on ANZCTR


Registration number
ACTRN12623000074695
Ethics application status
Approved
Date submitted
23/12/2022
Date registered
23/01/2023
Date last updated
10/12/2023
Date data sharing statement initially provided
23/01/2023
Date results information initially provided
26/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of AB-161 Following Oral Administration in Healthy Subjects
Scientific title
A Double-Blind, Randomized, Placebo-Controlled, Single Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AB-161 Following Oral Administration in Healthy Subjects
Secondary ID [1] 308635 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 328542 0
Condition category
Condition code
Infection 325558 325558 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product: AB-161
Dosage Formulation: Tablet
Route of Administration: Oral
Cohort 1: Participants will receive a single dose of 2.5 mg of AB-161 or placebo on Day 1
Cohort 2: Participants will receive a single dose of less than or equal to 7.5 mg of AB-161 or placebo on Day 1
Cohort 3: Participants will receive a single dose of less than or equal to 15 mg of AB-161 or placebo on Day 1
Cohort 4: Participants will receive a single dose of less than or equal to 25 mg of AB-161 or placebo on Day 1
Cohort 5: Participants will receive a single dose of less than or equal to 35 mg of AB-161 or placebo on Day 1
Cohort 6: The dose level will be based on safety and PK assessments of previous cohorts.
Cohort 7: The dose level will be based on safety and PK assessments of previous cohorts.
Cohort 8: The dose level will be based on safety and PK assessments of previous cohorts.
For each dosing cohort, 10 subjects will be randomized with 8 receiving AB-161 and 2 receiving placebo.
Subjects will receive a single morning dose of study treatment following an overnight fast of at least 10 hours. Dosing will be supervised in the clinic and compliance will be confirmed via mouth checks. Subjects will continue to fast for at least 4 hours after the dose.
Additionally, a single Food Effect assessment is to be conducted at a dose considered safe and well-tolerated. 10 subjects (8 active, 2 placebo) will receive a single dose of study treatment (AB-161 or placebo) on Day 1 following a high fat breakfast (approximately 1000 calories with 50%, 30%, and 20% of the calories derived from fat, carbohydrates, and protein, respectively). Subjects will have 30 minutes to complete the meal and the dose of AB-161 should be administered 30 minutes after the start of the meal. No food will be allowed for at least 4 hours post-dose.
Sentinel dosing of 2 subjects (1 active, 1 placebo) will occur at each dose level (except for the Food Effect panel). Dose escalation may occur after all available subjects have completed the treatment period and the Safety Review Committee (SRC) reviews all accumulated blinded safety and available PK data.
Each cohort will enrol a distinct group of subjects
Intervention code [1] 325097 0
Treatment: Drugs
Comparator / control treatment
Placebo tablets contain the same excipients used for the active drug product, but without addition of the spray dried intermediate containing drug substance.

Following an overnight fast of at least 10 hours, subjects participating in the food effect evaluation will receive a single dose of study treatment (AB-161 or placebo) on Day 1 following a high fat breakfast. Subjects will have 30 minutes to complete the meal and the dose of AB-161 should be administered 30 minutes after the start of the meal. No food will be allowed for at least 4 hours post-dose, after which subjects will be provided with a standard lunch.
Control group
Placebo

Outcomes
Primary outcome [1] 333399 0
To evaluate the safety and tolerability of AB-161 following oral administration of single doses to healthy subjects
To be assessed by monitoring
- The frequency and severity of treatment-emergent adverse events (TEAEs) will be coded to the Medical Dictionary for Regulatory Activities (MedDRA)
- Discontinuations due to adverse events (AEs) will be coded to the Medical Dictionary for Regulatory Activities (MedDRA)
- Laboratory (Clinical Chemistry, Hematology, Coagulation and Urinalysis): blood sample collection and analysis by pathology lab
- 12-lead Electrocardiogram (ECG)
- Vital sign abnormalities (systolic/diastolic BP - sphygmomanometer/blood pressure monitor; heart rate - stethoscope; respiratory rate - pulse oximeter; body temperature - thermometer)

The Investigator will assess intensity for each AE and SAE reported during the study using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Table)
Timepoint [1] 333399 0
- Adverse events monitored continuously from the time of dosing to 7 days post-dose, and then at 10 and 14 days post-dose
- Laboratory (Clinical Chemistry, Hematology, Coagulation and Urinalysis): Blood and urine samples collected on Day 1 pre-dose and 2 hours post dose, and at 2, 4, 6, 10 days post-dose.
- 12-lead Electrocardiogram (ECG) will be conducted at Baseline, Day 1, 2, 4, 6, 7 and 10.
- Vital sign monitored continuously from the time of dosing to 7 days post-dose, and then at 10 and 14 days post-dose
Secondary outcome [1] 416917 0
To characterize the single dose Pharmacokinetic (PK) of AB-161 in healthy subjects
Plasma and urine samples will be collected for PK analysis
Urine pharmacokinetics will only be assessed in Cohort 3.
PK parameters
- Maximum observed plasma concentration
- Time of maximum observed plasma concentration
- Area under the concentration time curve from the time of dosing to the last measurable concentration
- Area under the concentration time curve from the time of dosing extrapolated to infinity
- Plasma half life
- Apparent volume of distribution during terminal phase
- Apparent oral clearance
- Amount eliminated in the urine
- Renal clearance of unchanged drug in a specific interval (CLR[interval]) or cumulatively over all collection intervals, calculated as CLR = Ae/AUC where both Ae and AUC are determined over co-incident time ranges after dosing
Timepoint [1] 416917 0
Plasma PK sampling: Pre-dose (within 15 minutes prior to dosing), 1 hour post-dose, 2 hours post-dose, 3 hours post-dose, 4 hours post-dose, 6 hours post-dose, 8 hours post-dose, 10 hours post-dose, 12 hours post-dose, 16 hours post-dose, 24 hours post-dose, 48 hours post-dose, 72 hours post-dose

Urine PK sampling for Cohort 3: 0 – 6 hours post-dose, 6 – 12 hours post-dose, 12 – 24 hours post-dose, 24 – 48 hours post-dose, 48 – 72 hours post-dose

Eligibility
Key inclusion criteria
1. Subject must be 18 (or other appropriate age of consent) to 50 years of age, inclusive, at the time of signing the informed consent. Healthy subjects are defined as individuals free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.

2. Body mass index (BMI) more than 18 kg per meter square and less than 35 kg per meter square.

3. A male subject is eligible to participate if he does not have a female partner who is pregnant or who intends to become pregnant during the study. Male subjects must agree to use contraception as outlined in the protocol.

4. A female subject is eligible to participate only if she is a NOT a women of childbearing potential (WOCBP).

5. Ability to review and capable of giving signed informed consent which includes compliance with all protocol-specified visit schedules and requirements
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. A history of clinically significant endocrine, gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, cardiovascular, psychiatric or neurologic disorders.

2. Clinically significant ECG abnormalities, blood pressure or laboratory abnormalities, confirmed by repeat.

3. Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV confirmed by polymerase chain reaction (PCR). Evidence of prior HBV vaccination (positive HbsAb) is not exclusionary, and subjects with documented resolved HBV infection (HBsAg and HBV DNA negative) may participate.

4. Subjects who smoke or meet the protocol criteria for substance abuse.

5. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are WOCBP, pregnant or breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

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

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Study was discontinued due to a preclinical toxicology finding not related to peripheral neuropathy.
Date of first participant enrolment
Anticipated
16/03/2023
Actual
16/03/2023
Date of last participant enrolment
Anticipated
9/08/2023
Actual
19/04/2023
Date of last data collection
Anticipated
23/08/2023
Actual
10/05/2023
Sample size
Target
90
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 25186 0
New Zealand
State/province [1] 25186 0
Auckland

Funding & Sponsors
Funding source category [1] 312872 0
Commercial sector/Industry
Name [1] 312872 0
Arbutus Biopharma Corporation
Country [1] 312872 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arbutus Biopharma Corporation
Address
701 Veterans Circle,
Warminster, Pennsylvania,
United States, 18974
Country
United States of America
Secondary sponsor category [1] 314645 0
None
Name [1] 314645 0
Address [1] 314645 0
Country [1] 314645 0
Other collaborator category [1] 282523 0
Commercial sector/Industry
Name [1] 282523 0
Novotech (Australia) Pty Limited
Address [1] 282523 0
Level 3, 235 Pyrmont Street Sydney, NSW Australia - 2009
Country [1] 282523 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312150 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 312150 0
Ministry of Health, 133 Molesworth Street, PO Box 5013, Wellington, 6011
Ethics committee country [1] 312150 0
New Zealand
Date submitted for ethics approval [1] 312150 0
09/01/2023
Approval date [1] 312150 0
31/01/2023
Ethics approval number [1] 312150 0
2023 FULL 15063

Summary
Brief summary
The study drug AB-161 is being developed as a potential new treatment for chronic hepatitis B (CHB) infection. This is the first clinical study where AB-161 will be given to humans. The main goal is to determine whether AB-161 is safe and well tolerated when given at different doses. The levels of the study drug will also be measured at different times. The study may have up to 9 cohorts with 10 healthy volunteers per cohort. The first cohort will start with a conservative dose and dose escalation for each cohort will only occur after review of safety, tolerability, and pharmacokinetics data. The first two subjects in each cohort (except for the food effect panel) will be dosed in a 1:1 ratio of AB-161 to placebo. If the safety profile of the first two subjects is acceptable, the remainder of the subjects will be dosed in a 7:1 ratio of AB-161 to placebo. A separate dosing panel (food effect panel) will evaluate the effect food has on how AB-161 behaves in the body. Subjects will be dosed in a 8:2 ratio of AB-161 to placebo in the food effect panel. The food effect panel will be conducted after cohort 5 at a dose level considered safe and well tolerated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123658 0
Dr Edward John Gane
Address 123658 0
New Zealand Clinical Research, Ground Floor, 3 Ferncroft Street, Grafton, Auckland 1010 New Zealand
Country 123658 0
New Zealand
Phone 123658 0
+64021548371
Fax 123658 0
Email 123658 0
EdGane@adhb.govt.nz
Contact person for public queries
Name 123659 0
Mr Michael Child
Address 123659 0
Arbutus Biopharma Corporation,
701 Veterans Circle, Warminster,
Pennsylvania, United States, 18974
Country 123659 0
United States of America
Phone 123659 0
+12674690914
Fax 123659 0
Email 123659 0
clinicaltrials@arbutusbio.com
Contact person for scientific queries
Name 123660 0
Mr Michael Child
Address 123660 0
Arbutus Biopharma Corporation,
701 Veterans Circle, Warminster,
Pennsylvania, United States, 18974
Country 123660 0
United States of America
Phone 123660 0
+12674690914
Fax 123660 0
Email 123660 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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.