Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000709640
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 Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BW-20507 in Healthy Subjects
Scientific title
A Phase 1/2 Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BW-20507 in Healthy Subjects
Secondary ID [1] 309752 0
BW-20507-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12623000708651. These are two parts of the same study. The linked record is for the MAD arm of the study.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Virus (HBV) Infection 330152 0
Condition category
Condition code
Infection 327031 327031 0 0
Studies of infection and infectious agents
Oral and Gastrointestinal 327281 327281 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 active pharmaceutical ingredient (API) in water with necessary pH adjustment by NaOH or H3P04. 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 the study staff
The study will be conducted in 2 Parts:
• Part A: Single ascending dose (SAD) phase in healthy subjects where subjects will receive a single dose of either BW-20507 or placebo based on their assigned dose in cohort.
• Part B: Multiple ascending dose (MAD) phase in subjects with chronic HBV infection

PART A Cohorts are-
Cohort A1: A single 35mg dose of BW-20507 or placebo
Cohort A2: A single 100mg dose of BW-20507 or placebo
Cohort A3: A single 200mg dose of BW-20507 or placebo
Cohort A3: A single 400mg dose of BW-20507 or placebo
This registration is for the PART A of the study. Part B: Multiple ascending dose (MAD - registered in a separate form)
Intervention code [1] 326198 0
Treatment: Drugs
Comparator / control treatment
Part A is a placebo controlled study which will enrol subjects who will receive a single dose of either BW-20507 or placebo.
Placebo control agent will have the sodium chloride injection, 0.9%w/v) which will be administered as sub cutaneous injection(s).
Control group
Placebo

Outcomes
Primary outcome [1] 334897 0
Part A- To evaluate the safety and tolerability of a single dose of BW-20507 in healthy subjects.

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
- 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] 334897 0
Adverse events (AEs) and serious adverse events (SAEs): On day 1, day 2, day 3, day 8, day 15, day 22 and day 29 post dose administration.

Laboratory test: On screening, day -1, day 2, day 8, day 15, day 22 and day 29 post dose administration.

ECG: On screening, day -1, day 1, day 2, day 8 and day 29 post dose administration.

Vital Signs: -On screening, day-1 and day 1 vital signs will be measured pre-dose and at 1(±10 mins), 4(±15 mins), and 8(±30 mins) hours post-dose. Once daily on day 2, day 3, day 8, day 15, day 22 and day 29 post dose administration.

ISR- On day 1, day 2, day 3, day 8, day 15, day 22 and day 29 post dose administration.
Secondary outcome [1] 422365 0
Part A- To characterize the pharmacokinetics (PK) profile of a single dose of BW-20507 and its metabolites (if any) in healthy subjects.
Pharmacokinetoc 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 0 to infinity (AUC0-inf)
- urine concentration up to 24 hours post-dose.
Timepoint [1] 422365 0
PART A-
- Blood samples for PK analysis will be collected pre-dose and 0.5, 1, 2, 4, 8, 12, 21, 24, 48 and 168 hours post-dose.
- Urine samples for PK analysis will be collected pre-dose and 0-4, 4-12 and 12-24 hours post-dose.

Eligibility
Key inclusion criteria
Part A 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 60 aged years, inclusive, at the time of informed consent.
3. BMI (more than equal to) 18 and (less than equal to) 32 kg/m2 with body weight >50 and (less than equal to) 120 kg.
4. Triplicate 12-lead electrocardiogram (ECG) with normal limits or without clinically significant abnormalities* at screening and on Day -1, as determined by the Investigator.
5. 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 90 days following administration of the study drug as per study protocol.
6. Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception* from screening until 90 days following administration of the study drug as per protocol.

'clinically significant abnormalities*
Clinically significant ECG findings include, but are not limited to:
o QTcF interval > 450 ms (male) or 470 ms (female)
o QTcF interval < 340 ms
o PR interval < 120 ms
o PR interval > 220 ms, intermittent second or third-degree AV block, or AV
dissociation.
o RBBB, LBBB, IBBB, or IVCD

'effective methods of contraception* 'acceptable methods of contraception*
Hormonal methods of contraception including oral contraceptives containing combined estrogen and progesterone, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and progestogen-only hormonal contraception associated with inhibition of ovulation
o Nonhormonal intrauterine device (IUD)
o Bilateral tubal occlusion
o Vasectomised subject/partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner.
o True abstinence: when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception
For female subjects and female partners of subjects, hormonal contraceptives should begin at least 28 days prior to screening to ensure contraceptive is in full effect. Subjects will not be allowed to donate ova or sperm during the study.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
PART A Exclusion Criteria:
1. Any clinically significant medical condition or clinically significant abnormality in laboratory parameters that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
2. Hospitalization for any reason within 60 days prior to screening.
3. Any clinically significant acute condition such as fever (>38 degree celsius) or acute respiratory illness within 7 days of study drug administration.
4. Systolic blood pressure (more than equal to) 140 mmHg and/or diastolic blood pressure (more than equal to) 90 mmHg after at least 5 minutes resting (sitting or supine) at screening.
5. Any liver function panel analyte value >1.2 ×upper limits of normal (ULN) which includes aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at screening.
6. International normalized ratio (INR) above 1.5 at screening.
7. Calculated creatinine clearance (less than equal to) 60 mL/min (Cockcroft-Gault equation).
8. Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) prior to dosing or current participation in an investigational study.
9. Used prescription drugs, excluding oral contraceptive pills, within 14 days or 5 halflives (whichever is longer) before the dose of study drug.
10. Used over-the-counter medications, excluding routine vitamins and paracetamol, within 7 days or 5 half-lives (whichever is longer) before the dose of study drug, unless determined by the Investigator and Sponsor to be not clinically relevant.
11. Known history or test positive for HBsAg, hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. (Subjects with previous or treated hepatitis B or hepatitis C are not allowed to participate.)
12. Use of more than 10 tobacco/nicotine-containing products or equivalent per day within 30 days prior to screening.
13. History or clinical evidence of alcohol abuse, within the 12 months before screening. Alcohol abuse is defined as a regular weekly intake of more than 21 units for males and 14 units for females (unit: 1 glass of wine [125 mL] = 1 measure of spirits [30 mL] = one-half pint of beer [284 mL]).
14. History or clinical evidence of drug abuse, within the 12 months before screening. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms (in the judgement of the Investigator).
15. Positive test for alcohol or drugs of abuse at screening and Day -1.
16. History of allergic reaction to a synthetic small interfering RNA (siRNA) or Nacetylgalactosamine (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. Donated or lost >200 mL of blood within 30 days prior to screening.
19. With abdominal skin conditions such as tattoos, active skin diseases (inflammation, rashes, etc.) which in the opinion of the investigator may impact the subcutaneous administration of study drug and/or visibility of injection site reactions.
20. 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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation created by computer software(SASV9.4)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
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] 24808 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 40454 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 25561 0
Thailand
State/province [1] 25561 0
Country [2] 25562 0
Hong Kong
State/province [2] 25562 0

Funding & Sponsors
Funding source category [1] 313943 0
Commercial sector/Industry
Name [1] 313943 0
Argo Biopharma Australia Pty Ltd
Country [1] 313943 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] 315811 0
None
Name [1] 315811 0
Address [1] 315811 0
Country [1] 315811 0
Other collaborator category [1] 282689 0
Commercial sector/Industry
Name [1] 282689 0
Novotech(Australia) Pty Limited
Address [1] 282689 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009
Country [1] 282689 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313083 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 313083 0
Ethics committee country [1] 313083 0
Australia
Date submitted for ethics approval [1] 313083 0
17/05/2023
Approval date [1] 313083 0
30/06/2023
Ethics approval number [1] 313083 0
2023-05-560

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

Contacts
Principal investigator
Name 126938 0
Dr Jonathan Newchurch
Address 126938 0
CMAX Clinical Research
LEVEL 5 21-24 NORTH TERRACE, ADELAIDE South Australia 5000
Country 126938 0
Australia
Phone 126938 0
+61 8 7088 7900
Fax 126938 0
+61 8 7088 7999
Email 126938 0
[email protected]
Contact person for public queries
Name 126939 0
Xiafei Huang
Address 126939 0
Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 126939 0
China
Phone 126939 0
+86 21 50360208
Fax 126939 0
Email 126939 0
[email protected]
Contact person for scientific queries
Name 126940 0
Xiafei Huang
Address 126940 0
Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 126940 0
China
Phone 126940 0
+86 21 50360208
Fax 126940 0
Email 126940 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.