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Trial registered on ANZCTR


Registration number
ACTRN12623000708651
Ethics application status
Approved
Date submitted
12/06/2023
Date registered
3/07/2023
Date last updated
7/09/2023
Date data sharing statement initially provided
3/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Pharmacodynamics in Subjects with Chronic Hepatitis B Virus (HBV) Infection
Scientific title
A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Subjects with Chronic HBV Infection
Secondary ID [1] 309825 0
BW-20507-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12623000709640. They are two parts of the same study. The linked record is for the SAD arm of the study.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Virus (HBV) Infection 330241 0
Condition category
Condition code
Infection 327110 327110 0 0
Studies of infection and infectious agents
Oral and Gastrointestinal 327282 327282 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
BW-20507 injection is a sterile solution manufactured through dissolution of BW-20507 API in water with necessary pH adjustment by NaOH or H3P.  It will be supplied as a sterile 200 mg/1mL solution for SC injection.

BW-20507 (35, 100, 200, and 400 mg) or a matching placebo (sodium chloride injection, 0.9% w/v) will be administered as SC injection(s).
Investigational Product: BW-20507
Dosage Formulation: Solution
Route to Administration: Sub-cutaneous Injection which will be administered by study staff
The study will be conducted in 2 Parts:
• Part A: Subjects will receive a single dose of either BW-20507 or placebo based on their assigned dose in the cohort
• Part B: Multiple ascending dose (MAD) phase in subjects with chronic HBV infection where a group of subjects will receive multiple low doses of the drug and the dose is subsequently escalated for further groups, up to a predetermined level.

This registration is for PART B of the study. PART A Single Ascending dose (SAD-registered in a separate form)
- Cohorts 1b, 2b, and 4b will receive BW-20507 at three dose-levels of 100 mg, 200 mg, and 400 mg in subjects with chronic HBV infection on NUC therapy respectively. Cohort 3b will receive three doses of 200 mg of BW-20507 in subjects with chronic HBV infection not on NUC therapy (NUC naïve). Cohort 3b will start NUC therapy based on the Principal Investigator discretion on Day 1.
- Method of allocation: Cohorts 1b to 4b will each enroll a minimum of 6 and a maximum of 8 subjects with chronic HBV infection in an open-label fashion to receive three doses of BW-20507 (Day 1, Day 29, Day 57).

The doses for MAD protocol will be determined based on safety and pharmacokinetic data from Part A, etc.
Intervention code [1] 326257 0
Treatment: Drugs
Comparator / control treatment
All cohorts in Part B will be directly compared against each other, etc.
Control group
Dose comparison

Outcomes
Primary outcome [1] 334980 0
Part B- To evaluate the safety and tolerability of multiple doses of BW-20507 in subjects with chronic hepatitis B virus (HBV) infection.
To be assessed by monitoring-.
- Adverse events (AEs) and serious adverse events (SAEs) will be coded using the latest version of Medical Dictionary for Regulatory Activities (MedDRA)
- Clinical laboratory findings ( Hematology, blood Chemistry, Coagulation and urinalyis): blood and urine sample collection and analysis by local laboratory.
- 12-lead Electrocardiogram (ECG)
- Vital sign measurements of systolic/diastolic blood pressure, Heart rate, body temperature and respiratory rate using standard manual or electronic clinical procedures.
- Injection site reactions (ISR) will be monitored by physical examination and evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V5.
Timepoint [1] 334980 0
Adverse events (AEs) and serious adverse events (SAEs): From day 1 to day 337 post first dose.

Laboratory test: On screening, and then 4 hours post-dose on each of day 1, day 2, day 8. day 15, day 29, day 43, day 57, day 71, day 85, day 113. day 141, day 169, day 225, day 281 and day 337 post first dose administration.

ECG: On screening, day 1, day 2, day 29 and day 57 post first dose administration.

Vital Signs: On Day 1 vital signs will be measured pre-dose and 4 hours post-dose. Once daily on day 2, day 8, day 15, day 29, day 43. day 57. day 71, day 85, day 113 and day 141 post first dose administration

ISR- On day 1, day 2, day 8. day 15. day 29. day 43. day 57 and day 71 post first dose administration.
Secondary outcome [1] 422616 0
Part B- To characterize the PK profile of multiple doses of BW-20507 and its metabolites (if any) in subjects with chronic HBV infection.

Pharmacokinetic Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Terminal elimination Half-life (t½)
- Area under the plasma concentration versus time curve from zero to 24 hours (AUC0-24)
- AUC from time o to infinity (AUCo-inf)
Timepoint [1] 422616 0
PART B­
Blood samples for PK analysis will be collected pre-dose and 1,2,4, 8 24, and 168 hrs post first dose on Day 1: Pre-dose and 1, 2, 4, and 8 hours post second dose on Day 29 and post third dose on Day 57.
Secondary outcome [2] 422617 0
PART B­
To assess the reduction of HBsAg from Day 1, pre-dose baseline to post-dose nadir in
response to BW-20507 in subjects with chronic HBV infection.

Parameters assessed-
Serum samples to assess the HBsAG decrease log10 from Baseline (BS)
Timepoint [2] 422617 0
Blood samples to check the virology will be collected once daily on day 1, day 8, Day 15, day 29, day 43, day 57 post-first dose (treatment period); day 71, day 85. day 113, day 141 post-first dose (post treatment follow up phase) and day 169, day 225. day 281 and day 337 post-first dose (extended follow-up period).

Eligibility
Key inclusion criteria
PART B Inclusion Criteria:
Subjects must meet all the following criteria to be eligible to participate in the study.
1. Must have given written informed consent and be able to comply with all study requirements.
2. Males or females aged 18 to 65 aged years, inclusive, at the time of informed consent.
3. BMI (more than and equal to) 18 and (less than equal to) 32 kg/m2 with body weight >50 kg at screening.
4. Chronic HBV infection as defined by a positive serum HBsAg for (more than equal to) 6 months at screening.
5. On nucleotide/nucleoside analogs (NUC) therapy for at least 6 months without an interruption of 7 or more consecutive days at screening (Not applicable for NUC naive subjects)
6. NUC naive at screening (Only for NUC naive subjects).
7. HBSAg >50 IU/mL at screening.
8. HBV DNA <9o IU/mL at screening (Not applicable for NUC naive subjects).
9. Triplicate 12-lead electrocardiogram(ECG) with normal limits or without clinically significant abnormalities· at screening, as determined by the Investigator.
10. Female subjects must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant. with male partners, can participate if they are using highly effective methods of contraception· from 28 days prior to screening until go days following last administration of the study drug and use contraceptive as per study protocol..
11. Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception from study drug administration until go days following last administration of the study drug and use contraceptives as per study protocol.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
PART B Exclusion Criteria:
1. Any clinically significant chronic medical condition other than chronic HBV infection or clinically significant abnormality in laboratory parameters not related to chronic HBV infection that. in the opinion of the Investigator, makes the participant unsuitable for participation in the study.
2. Any clinically significant acute condition such as fever (>38 degree celsius) or acute respiratory illness within 7 days of study drug administration.
3. Significant liver fibrosis or cirrhosis as defined by having either a FibroScan result of > 8.5kPa at screening or a liver biopsy within 1 year with Metavir F3 fibrosis or F4 cirrhosis.
4. Subject has the following laboratory parameters at screening (by local laboratory):
- INR > 1.2 x ULN
- serum ALT or AST > 2 ULN
Study laboratory tests may be repeated once (eg, for values thought to be erroneous).
5. Active infection with HCV, hepatitis Delta virus (HDV), or HIV at screening.
6. Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
7. Used prescription drugs within 14 days or 5 half-lives (whichever is longer) before study drug administration except for a stable dose of: medication to treat hypertension, inhaler or nebulizer to treat asthma, hormone replacement therapy, antihistamines, and contraceptive therapy. Hypertension must be well controlled on no more than 2 medications or 1 medication with two active components for >6 months. Asthma must be well controlled, requiring, on average, use of a rescue bronchodilator no more than twice per week.
8. Over-the-counter medications, excluding routine vitamins and paracetamol, within 7 days or 5 half-lives (whichever is longer) before study drug administration, unless determined by the Investigator and Sponsor to be not clinically relevant. and unlikely to interfere with study conduct. and unlikely to interfere with study conduct.
9. Consume more than 7 units of alcohol per week within one month before screening (unit: 1 glass of wine [125 mL = 1 measure of spirits [30 mL = one-half pint of beer [284 mL]). Alcohol is limited to no more than 1 unit per day for the duration of the study.
10. History or clinical evidence of alcohol or drug abuse, within the 12 months before screening or a positive test for alcohol or drugs of abuse at screening.
11. Calculated creatinine clearance (less than equal to) 60 ml/min (Cockcroft-Gault equation).
12. History of chronic liver disease from any cause other than chronic HBV infection.
13. Diagnosed or suspected hepatocellular carcinoma.
14. History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices
15. Currently taking, or has taken within 12 months of screening, any interferon-containing therapy.
16. History of allergic reaction to a siRNA or GalNAc.
17. Have received vaccination with a live vaccine (except for influenza vaccine) during the past 4 weeks before Screening or have the intention to receive a live vaccine during the study period. NOTE: Receipt of
inactivated vaccines (inactivated influenza vaccines and approved COVID-19 vaccines) is not considered exclusionary if received at least 7 days prior to study drug administration.
18. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.

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
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/08/2023
Actual
2/08/2023
Date of last participant enrolment
Anticipated
30/11/2023
Actual
Date of last data collection
Anticipated
30/04/2024
Actual
Sample size
Target
32
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 24864 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 40512 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 25576 0
Thailand
State/province [1] 25576 0
Country [2] 25577 0
Hong Kong
State/province [2] 25577 0

Funding & Sponsors
Funding source category [1] 314010 0
Commercial sector/Industry
Name [1] 314010 0
Argo Biopharma Australia Pty Ltd
Country [1] 314010 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Argo Biopharma Australia Pty Ltd
Address
Level 5, 63 Pirie Street, Adelaide, SA, 5000, Australia
Country
Australia
Secondary sponsor category [1] 316048 0
None
Name [1] 316048 0
Address [1] 316048 0
Country [1] 316048 0
Other collaborator category [1] 282693 0
Commercial sector/Industry
Name [1] 282693 0
Novotech(Australia) Pty Limited
Address [1] 282693 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009
Country [1] 282693 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313147 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 313147 0
Ethics committee country [1] 313147 0
Australia
Date submitted for ethics approval [1] 313147 0
17/05/2023
Approval date [1] 313147 0
30/06/2023
Ethics approval number [1] 313147 0
2023-05-560

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127154 0
Dr Jonathan Newchurch
Address 127154 0
CMAX Clinical Research
LEVEL 5 21-24 NORTH TERRACE, ADELAIDE South Australia 5000
Country 127154 0
Australia
Phone 127154 0
+61 8 7088 7900
Fax 127154 0
+61 8 7088 7999
Email 127154 0
[email protected]
Contact person for public queries
Name 127155 0
Xiafei Huang
Address 127155 0
Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 127155 0
China
Phone 127155 0
+86 21 50360208
Fax 127155 0
Email 127155 0
[email protected]
Contact person for scientific queries
Name 127156 0
Xiafei Huang
Address 127156 0
Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 127156 0
China
Phone 127156 0
+86 21 50360208
Fax 127156 0
Email 127156 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.