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Trial registered on ANZCTR


Registration number
ACTRN12619001255178
Ethics application status
Approved
Date submitted
16/08/2019
Date registered
11/09/2019
Date last updated
18/11/2019
Date data sharing statement initially provided
11/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the Safety, Tolerability, and Pharmacokinetics of AB-506 in Healthy Subjects for 28 Days
Scientific title
A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AB-506, an HBV Capsid Inhibitor, in Healthy Caucasian and East Asian Subjects for 28 Days
Secondary ID [1] 298850 0
AB-506-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Infection (CHB) 313811 0
Condition category
Condition code
Infection 312220 312220 0 0
Other infectious diseases
Oral and Gastrointestinal 312618 312618 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
This study will be a Phase 1, double blind, randomized, placebo-controlled, multiple dose study to investigate the safety, tolerability, and PK of orally administered multiple doses of AB-506 to healthy subjects for 28 days.
Two unique cohorts of 14 healthy subjects, one Caucasian (Cohort A) and one East Asian (Cohort B): AB-506 or placebo will be administered once daily (10:4 ratio AB-506:placebo) for 28 days.
Each subject will participate in a screening visit and will receive 400mg AB-506 orally once daily for 28 days, with follow-up visits 4, 7 and 14 days after last dose. Adherence to the intervention is monitored by instructing the subjects to bring all unused study medication containers to each treatment period visit, as well as any empty bottles. The dates and number of tablets dispensed and returned must be recorded on the drug accountability form maintained on-site. Subjects will be instructed to record their study drug dosing in a dosing diary, which will be reviewed at each visit, in combination with drug accountability to confirm treatment compliance. Sites should discuss with the subject if there are discrepancies between the diary and the drug log to reconcile actual dosing at each visit.
Intervention code [1] 315153 0
Treatment: Drugs
Comparator / control treatment
Placebo to match AB-506 will be used. The use of a placebo for AB-506 in this study will ensure an adequate assessment of safety and tolerability of AB-506 in healthy subject cohorts. The placebo tablets contain the same excipients used for the active drug product (AB-506), but without addition of the spray dried intermediate containing drug substance which is replaced by Microcrystalline Cellulose and Mannitol.
Control group
Placebo

Outcomes
Primary outcome [1] 320903 0
To evaluate the safety and tolerability of AB-506 following oral administration of once daily multiple doses for 28 days to healthy subjects as assessed by frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities, after once daily multiple doses of AB-506 for 28 days
Timepoint [1] 320903 0
Adverse events will be collected from the time of the start of study treatment through the Day 42 visit. Serious adverse events will be collected from the signing of the informed consent form through the Day 42 visit and followed until resolution of any event. The dose of 400 mg once daily over 10 days of dosing was assessed previously in healthy subjects as part of the ongoing first-in-human study AB-506-001. All adverse events at this dose were assessed as unrelated and were mild. The most frequently observed event regardless of relatedness was headache. Adverse events will be assessed by clinical site staff during clinic visits by clinical examination and by participant self-reporting.
The lab abnormalities are assessed during clinical lab tests such as hematology, clinical chemistry, coagulation tests, serology, and urine parameters performed at Screening, Day -1, 4, 7, 10, 14, 18, 21, 24, 28, 32, 35 and 42.
Secondary outcome [1] 373302 0
To characterize the single dose PK of AB-506 in healthy subjects over 28 days. PK parameters include maximum observed plasma concentration [Cmax], time of maximum observed plasma concentration [Tmax], area under the concentration-time curve from time 0 to the end of the dosing period [AUCTAU], and plasma concentration at end of the dosing interval [CTAU]) of AB-506 in healthy subjects; predose plasma concentration (Ctrough) will also be evaluated at multiple timepoints.
Timepoint [1] 373302 0
Days 1 and 28: Pre-dose (within 15 minutes prior to dosing), 1 hour, 2 hour, 4 hour, 6 hour, 12 hour, 24 hours post dose.
Days 7, 14, and 21: Pre-dose (within 15 minutes prior to dosing)
For subjects who discontinue treatment early, a single PK sample will be obtained if possible.
Secondary outcome [2] 374539 0
To characterize the steady-state PK of AB-506 in healthy subjects over 28 days. PK parameters include maximum observed plasma concentration [Cmax], time of maximum observed plasma concentration [Tmax], area under the concentration-time curve from time 0 to the end of the dosing period [AUCTAU], and plasma concentration at end of the dosing interval [CTAU]) of AB-506 in healthy subjects; predose plasma concentration (Ctrough) will also be evaluated at multiple timepoints.
Steady state of AB-506 following multiple dose administration will be assessed visually through time-concentration plots of the trough concentration data.
Timepoint [2] 374539 0
Days 1 and 28: Pre-dose (within 15 minutes prior to dosing), 1 hour, 2 hour, 4 hour, 6 hour, 12 hour, 24 hours post dose.
Days 7, 14, and 21: Pre-dose (within 15 minutes prior to dosing)
For subjects who discontinue treatment early, a single PK sample will be obtained if possible.

Eligibility
Key inclusion criteria
To be eligible for enrolment into this study, subjects must meet all of the inclusion criteria for cohort in which they are enrolled:
1. Healthy males or females aged 18–45, inclusive.
2. Subjects must be either White/Caucasian or East Asian
3. Male subjects must agree to use contraception as detailed in the protocol.
4. A female subject is eligible to participate if she is not pregnant, not breastfeeding, does not intend to become pregnant during the study, and at least one of the following conditions applies:
a. Not a woman of childbearing potential OR
b. A woman of childbearing potential who agrees to follow the contraceptive guidance starting 4 weeks prior to the first dose of study drug, during the treatment period, and for 30 days after the last dose of study treatment.
5. Body mass index (BMI) greater than or equal to 18 kg/m2 and less than or equal to 28 kg/m2.
6. Capable of giving signed informed consent, able to understand and comply with protocol requirements, instructions, and protocol-related restrictions, and likely to complete the study as planned.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
To be eligible for enrolment into this study, subjects must not meet any of the exclusion criteria for the cohort in which they are enrolled:
Medical Status or History;
1. A history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, or cardiovascular disease.
2. Evidence of active or suspected malignancy, or a history of malignancy.

Findings/Diagnostic Assessments;
1. Clinically significant ECG or Vital Signs abnormalities at Screening, Day -1, or Day 1 pre-dose
2. Clinically significant abnormalities in laboratory test results at Screening or Day -1
3. ALT or AST > upper limit of normal (ULN) confirmed by a repeat reading.
4. Estimated creatinine clearance <80 mL/min
5. Positive serology for HBV, hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
6. Subjects meeting any of the following criteria for substance abuse potential:
a. Subjects with a clinical history of or current heavy drinking.
b. Positive alcohol test (breath, saliva, or urine) at Screening or Day -1.
c. Positive urine test for drugs of abuse at Screening or Day -1.

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)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No hypothesis will be formally tested in the study. Approximately 56 healthy subjects will be screened to achieve approximately 28 randomized subjects. Subjects who discontinue may be replaced.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Arbutus Biopharma decided to discontinue development of AB-506 as two cases of acute hepatitis were observed in this clinical trial.
Date of first participant enrolment
Anticipated
11/09/2019
Actual
11/09/2019
Date of last participant enrolment
Anticipated
21/09/2019
Actual
21/09/2019
Date of last data collection
Anticipated
1/11/2019
Actual
24/10/2019
Sample size
Target
28
Accrual to date
Final
28
Recruitment outside Australia
Country [1] 21731 0
New Zealand
State/province [1] 21731 0
Auckland

Funding & Sponsors
Funding source category [1] 303398 0
Commercial sector/Industry
Name [1] 303398 0
Arbutus Biopharma Corporation
Country [1] 303398 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arbutus Biopharma Corporation
Address
701 Veterans Circle
Warminster, PA 18974
Country
United States of America
Secondary sponsor category [1] 303439 0
None
Name [1] 303439 0
Address [1] 303439 0
Country [1] 303439 0
Other collaborator category [1] 280885 0
Commercial sector/Industry
Name [1] 280885 0
Novotech (Australia) Pty Limited
Address [1] 280885 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280885 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303927 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 303927 0
Ministry of Health, Health and Disability Ethics Committees, 133 Molesworth Street, Thorndon, Wellington 6011
Ethics committee country [1] 303927 0
New Zealand
Date submitted for ethics approval [1] 303927 0
12/07/2019
Approval date [1] 303927 0
02/08/2019
Ethics approval number [1] 303927 0
19/CEN/120

Summary
Brief summary
This is a Phase 1, double blind, randomized, placebo-controlled, multiple dose study to investigate the safety, tolerability, and PK of orally administered multiple doses of AB-506 to healthy subjects for 28 days.
The purpose of this study will be to explore the safety, tolerability, and PK of multiple doses of AB-506 in Caucasian and East Asian healthy subjects for 28 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95282 0
Prof Edward Gane
Address 95282 0
Auckland Clinical Studies Ltd and Auckland City Hospital, PO Box 8963, Symonds St, Auckland, 1150
Country 95282 0
New Zealand
Phone 95282 0
+64 21548371
Fax 95282 0
Email 95282 0
[email protected]
Contact person for public queries
Name 95283 0
Michael Child
Address 95283 0
Arbutus Biopharma Corporation
701 Veterans Circle
Warminster, Pennsylvania
United States , 18974
Country 95283 0
United States of America
Phone 95283 0
+1 267 469 0914
Fax 95283 0
Email 95283 0
[email protected]
Contact person for scientific queries
Name 95284 0
Michael Child
Address 95284 0
Arbutus Biopharma Corporation
701 Veterans Circle
Warminster, Pennsylvania
United States , 18974
Country 95284 0
United States of America
Phone 95284 0
+1 267 469 0914
Fax 95284 0
Email 95284 0
[email protected]

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.