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Trial registered on ANZCTR


Registration number
ACTRN12617000557336
Ethics application status
Approved
Date submitted
1/04/2017
Date registered
21/04/2017
Date last updated
17/08/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to determine the safety and anti-viral activity of ARB-1740 in patients with chronic hepatitis B virus (HBV) infection.
Scientific title
A Phase 1a/1b, Blinded, Randomized, Placebo-Controlled Study Evaluating the Safety, Anti-Viral Activity, and Pharmacokinetics of ARB-1740 in Non Cirrhotic, HBV-DNA Negative and Positive Subjects with Chronic HBV Infection.
Secondary ID [1] 291420 0
Arbutus Biopharma Protocol Number: ARB-1740-001
Universal Trial Number (UTN)
U1111-1194-0491
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic hepatitis B virus infection 302434 0
Condition category
Condition code
Infection 302003 302003 0 0
Other infectious diseases
Oral and Gastrointestinal 302260 302260 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
Intervention name: ARB-1740 for the treatment of chronic hepatitis B virus infection.

Intervention description: Approximately 30 HBeAg-negative, non–cirrhotic subjects will be enrolled in three sequential cohorts; each cohort will include approximately 10 subjects, randomized 4:1 to treatment with ARB-1740 or placebo.

Cohort 1 (0.05 mg/kg): All subjects will be HBV-DNA Positive and either treatment experienced or treatment naive.

Cohort 2 (0.1 mg/kg) and Cohort 3 (0.2 mg/kg): All subjects will be virally suppressed (HBV-DNA Negative), and receiving nucleos(t)ide analogue (NA) therapy for at least 12 months. A premedication regimen will be used prior to each dose of ARB-1740. Briefly: anti-inflammatory medication will be administered 8-12 hours prior to study treatment infusion; anti-inflammatory and antihistamine medication will be administered 30 minutes prior to study treatment infusion.

For each cohort, ARB-1740 or placebo will be administered as a 2-hour intravenous infusion. Subjects will receive ARB-1740 or placebo on Days 1, 29 and 57 (End of Treatment [EOT] Visit). All subjects will be followed for at least 24 weeks after the EOT Visit.

At each visit, subjects will be asked by the site personnel about their state of health and use of any concomitant medication since Screening or since the previous study visit. They will also be questioned about their adherence with study restrictions.
Intervention code [1] 297454 0
Treatment: Drugs
Comparator / control treatment
The control treatment is normal saline for injection (0.9% NaCl), administered in the same manner as the investigational drug product.
Control group
Placebo

Outcomes
Primary outcome [1] 301430 0
Composite Primary Outcome: The frequency and severity of treatment-emergent adverse events (AEs), discontinuations due to AEs, and laboratory abnormalities, by cohort, in HBV-DNA Negative (-) subjects, assessed through continuous monitoring by the Investigator.

Possible AEs may include infusion related reactions, cytokine release syndrome, or anaphylactic reactions. The Investigator is responsible for the detection and documentation of AEs, and assessment of severity and causality.

Abnormal laboratory findings (e.g., clinical chemistry, hematology, urinalysis, complement, cytokines) or other abnormal assessments (e.g., ECGs and vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs.

Discontinuation: The Investigator is responsible for determining if any AE or laboratory abnormality indicates that continued participation in the study is not in the best interest of the subject.
Timepoint [1] 301430 0
Monitored over the course of the study, through 28 days after the last infusion of study treatment.
Secondary outcome [1] 332607 0
Composite Secondary Outcome: The frequency and severity of treatment-emergent AEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, in HBV-DNA Positive (+) subjects, assessed through continuous monitoring by the Investigator.

Possible AEs may include infusion related reactions, cytokine release syndrome, or anaphylactic reactions. The Investigator is responsible for the detection and documentation of AEs, and assessment of severity and causality.

Abnormal laboratory findings (e.g., clinical chemistry, hematology, urinalysis, complement, cytokines) or other abnormal assessments (e.g., ECGs and vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs.

Discontinuation: The Investigator is responsible for determining if any AE or laboratory abnormality indicates that continued participation in the study is not in the best interest of the subject.
Timepoint [1] 332607 0
Monitored over the course of the study, through 28 days after the last infusion of study treatment.
Secondary outcome [2] 332608 0
ARB-1740 pharmacokinetic parameters including maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), and area under the plasma concentration-time curve from the start of infusion to the last measurable concentration (AUC0-t) assessed by plasma analysis.
Timepoint [2] 332608 0
For Dose 1 and Dose 3: Samples are taken pre-dose, at the end of infusion (EOI), and then at 0.25, 0.5, 2, 4, 6, 24, and 168 hours post-EOI. For Dose 2: Samples are taken pre-dose and at EOI.
Secondary outcome [3] 332609 0
HBV surface antigen (HBsAg) levels in virally suppressed [HBV-DNA(-)] subjects, assessed by blood tests.
Timepoint [3] 332609 0
Samples will be taken on Days 2, 8, 15, 22, 30, 43, 58, 64, 71, Follow-up (FU) Week 4, FU Week 12, FU Week 24 (FU Week 24 for Cohort 1 only).

Eligibility
Key inclusion criteria
1. Chronic HBV infection as documented at screening by either:
i. Positive HBsAg or HBeAg or HBV-DNA at least 6 months prior to screening; OR
ii. Historical liver biopsy consistent with chronic HBV infection at screening.
2. Quantitiative HBsAg greater than or equal to 1000 IU/mL at the Screening Visit.
3. For Cohorts 2 and 3: Subjects currently receiving entecavir and/or tenofovir for greater than or equal to 12 months and HBV-DNA undetectable.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known co-infection with HIV, hepatitis C virus, or hepatitis D virus.
2. 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.

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)
Interactive Response Technology (IRT) system (ie. Central randomisation by phone/fax/computer).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table generated by an independent statistician and programmed within the IRT system.
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
No formal statistical hypotheses will be tested. Enrollment of 10 patients per cohort with 4:1 randomization to treatment with ARB-1740 or placebo will allow the safety and tolerability of ARB-1740 to be determined.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Study ARB-1740-001 will be stopped prematurely. Preliminary data posed no safety concerns, however Arbutus is discontinuing development of ARB-1740.
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 outside Australia
Country [1] 8729 0
New Zealand
State/province [1] 8729 0
Country [2] 8731 0
Moldova, Republic Of
State/province [2] 8731 0
Country [3] 8732 0
Singapore
State/province [3] 8732 0
Country [4] 8733 0
Romania
State/province [4] 8733 0

Funding & Sponsors
Funding source category [1] 295890 0
Commercial sector/Industry
Name [1] 295890 0
Arbutus Biopharma Corporation
Address [1] 295890 0
100-8900 Glenlyon Parkway
Burnaby, British Columbia
V5J-5J8
Country [1] 295890 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Arbutus Biopharma Corporation
Address
100-8900 Glenlyon Parkway
Burnaby, British Columbia
V5J-5J8
Country
Canada
Secondary sponsor category [1] 294760 0
None
Name [1] 294760 0
Address [1] 294760 0
Country [1] 294760 0
Other collaborator category [1] 279476 0
Commercial sector/Industry
Name [1] 279476 0
WCCT Global, Inc.
Address [1] 279476 0
2300 E. Lincoln Hwy, Suite 714
Langhorne, PA 19047
Country [1] 279476 0
United States of America
Other collaborator category [2] 279477 0
Commercial sector/Industry
Name [2] 279477 0
ARENSIA Exploratory Medicine GmbH
Address [2] 279477 0
Merowingerplatz 1
40225 Dusseldorf
Country [2] 279477 0
Germany
Other collaborator category [3] 279478 0
Commercial sector/Industry
Name [3] 279478 0
CBR Biotech Strategies GmbH
Address [3] 279478 0
Tegeler Strasse 7
13353 Berlin
Country [3] 279478 0
Germany
Other collaborator category [4] 279479 0
Commercial sector/Industry
Name [4] 279479 0
Auckland Clinical Studies, Ltd.
Address [4] 279479 0
3 Ferncroft St. Grafton
Auckland, 1010
Country [4] 279479 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297168 0
National Committee for Ethical Expertise of Clinical Trial
Ethics committee address [1] 297168 0
MD 2009, Chisinau municipality, 3 A. Cosmescu Street
Ethics committee country [1] 297168 0
Moldova, Republic Of
Date submitted for ethics approval [1] 297168 0
10/11/2016
Approval date [1] 297168 0
07/12/2016
Ethics approval number [1] 297168 0
NCEECT/262/30.11.2016
Ethics committee name [2] 297169 0
National Healthcare Group Domain Specific Review Board
Ethics committee address [2] 297169 0
Nexus @One-North (South Tower),
No. 3 Fusionopolis Link,
#03-08, Singapore 138543
Ethics committee country [2] 297169 0
Singapore
Date submitted for ethics approval [2] 297169 0
01/11/2016
Approval date [2] 297169 0
10/01/2017
Ethics approval number [2] 297169 0
2016/01193

Summary
Brief summary
The purpose of this study is to determine the safety of ARB-1740 in patients with chronic hepatitis B, and the best dose of ARB-1740. This includes looking at any side effects or health problems that might occur after ARB-1740 is given, as well as changes to HBV infection. Another purpose is to see how ARB-1740 behaves in the body, including the way the drug is absorbed (taken up) by the body. Three doses of ARB-1740 or placebo (a treatment that looks like ARB-1740 but does not contain any drug) will be given over eight weeks. The doses with be given intravenously (through a small tube into a vein in the arm). Subjects will have an 80% chance of receiving ARB-1740, and 20% chance of receiving placebo. Group 1 of the study enrolled patients with virus that can be detected., These subjects received placebo or ARB-1740 at 0.05 mg/kg. Enrollment of this group is complete. Group 2 and Group 3 of this study will enroll subjects already taking nucleos(t)ide analogue treatment for chronic hepatitis B virus infection, with no measurable virus. Subjects in Groups 2 and 3 will receive some medication to prevent allergic reactions before being treated with placebo or ARB-1740 at 0.1 mg/kg (Group 2) or ARB-1740 at 0.2 mg/kg (Group 3).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73214 0
Prof Edward Gane
Address 73214 0
Auckland Clinical Studies, Ltd.
3 Ferncroft St. Grafton
Auckland, 1010
Country 73214 0
New Zealand
Phone 73214 0
+64 9 373 3474
Fax 73214 0
+64 9 373 3479
Email 73214 0
EdGane@adhb.govt.nz
Contact person for public queries
Name 73215 0
Ms Susan Oakley
Address 73215 0
Arbutus Biopharma Corporation
100-8900 Glenlyon Parkway
Burnaby, BC
V5J5J8
Country 73215 0
Canada
Phone 73215 0
+1 604 4566008
Fax 73215 0
+1 604 4193201
Email 73215 0
soakley@arbutusbio.com
Contact person for scientific queries
Name 73216 0
Ms Jill Denning
Address 73216 0
Arbutus Biopharma, Inc.
3805 Old Easton Road
Doylestown, PA
18902
Country 73216 0
United States of America
Phone 73216 0
+1 416 9130676
Fax 73216 0
+1 604 4193201
Email 73216 0
jdenning@arbutusbio.com

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary