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Trial registered on ANZCTR


Registration number
ACTRN12623000689673
Ethics application status
Approved
Date submitted
8/06/2023
Date registered
26/06/2023
Date last updated
31/08/2023
Date data sharing statement initially provided
26/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BW-20805 in Healthy Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered BW-20805 in Healthy Subjects
Secondary ID [1] 309780 0
BW-20805-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary angioedema 330184 0
Condition category
Condition code
Human Genetics and Inherited Disorders 327061 327061 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BW-20805 is a clear, colorless to yellow solution. It will be supplied as a sterile 200 mg/1mL solution for subcutaneous (SC) injection. BW-20805 (50mg, 150mg, 300mg, 600 mg) or matching placebo (sodium chloride injection, 0.9% w/v) will be administered as SC injection(s).
This study will consist of 4 separate and sequential dose cohorts. Within each cohort, 8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20805 (n=6) or placebo (n=2). The population in Cohort 1 to 4 will include healthy subjects.
- Cohort 1: 50 mg BW-20805 or placebo
- Cohort 2: 150 mg BW-20805 or placebo
- Cohort 3: 300 mg BW-20805 or placebo
- Cohort 4: 600 mg BW-20805 or placebo
Each cohort will firstly enroll a sentinel group of 2 subjects, of which one will receive BW-20805 and the other will receive placebo in a double-blind fashion. If deemed safe and tolerated by the Investigator, the remaining subjects in the same cohort will be dosed after the 2nd sentinel subject through 48 hours post dosing.
Dose escalation will be based on the Safety Review Committee (SRC) assessment.
The doses will be administered by the study nurse(s) or trained staff at site.
Accurate records will be kept by the unblinded pharmacy personnel or designee(s) of when and how much study drug is dispensed and used by each subject in the study. Any reason for departure from the protocol-specified dispensing regimen must also be recorded. Destruction and return should also be recorded. Study drug accountability records will be maintained by the unblinded pharmacy personnel or designee(s) in a secure location. Drug accountability records will be available for verification by Argo Biopharma personnel or designee.
Intervention code [1] 326259 0
Treatment: Drugs
Comparator / control treatment
Placebo
Sodium chloride injection (0.9% w/v) will be administered via subcutaneous injection.
Control group
Placebo

Outcomes
Primary outcome [1] 334982 0
The primary outcomes are to evaluate the safety and tolerability of a single dose of BW-20805 in healthy subject. Safety assessment will be AEs and clinical assessments including but not limited to laboratory test results.
- AEs will be categorized with the use of the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of AEs will be summarized by system organ class, preferred term, and treatment group.
- Safety laboratory assessments by collection of blood sample for assessment of chemistry and hematology, serology (HIV antibody, HBsAg, anti-Hbc, and anti-HCV at screening), coagulation and urine sample for urinalysis. The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline.
- Vital signs (blood pressure, heart rate, temperature, and respiratory rate) and 12-lead ECGs (heart rate, PR interval, QRS interval, QT, and QTc interval) will also be summarized by visit and by treatment group, along with the changes from baseline. Abnormal physical examination findings will be listed. Vital signs assessed by vital signs monitor (vital signs monitor can simultaneously monitor blood pressure, heart rate, respiratory rate, and temperature).
Timepoint [1] 334982 0
AEs: Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day85, Day 127 and Day169 post-dose.
Laboratory test, Vital signs, and 12-lead ECGs: Screening, Day-1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day85, Day 127 and Day169 post-dose.
Secondary outcome [1] 422687 0
To characterize the pharmacokinetics (PK) of a single dose of BW-20805 and its metabolites (if any) in healthy subjects. PK parameters include, but are not limited to,
- maximum observed plasma concentration (Cmax),
- time to maximum plasma concentration (Tmax),
- terminal elimination half-life (t1/2),
- area under the plasma concentration versus time curve from zero to 48 hours (AUC0-48),
- area under the plasma concentration versus time curve from zero to infinity (AUC0-inf),
- urine concentration up to 24 hours post-dose.
Timepoint [1] 422687 0
PK blood samples will be collected within 1 hour pre-dose and 0.5, 1, 2, 4, 8,12, 21 and 24 hours post-dose.
Pooled urine samples for PK will be collected at pre-dose, 0-4 hours, 4-12 hours and 12-24 hours intervals post-dose.
Secondary outcome [2] 422688 0
To characterize the pharmacodynamics (PD) of a single dose of BW-20805 and its metabolites (if any) in healthy subjects by collection of blood sample for assessment.
- Plasma PKK concentration
- Plasma proenzyme activation
- Cleaved high molecular weight kininogen (HMWK)
Timepoint [2] 422688 0
Screening visit, Day -1, Day1 (pre-dose), Day 3, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day85, Day 127 and Day169 post-dose.
Secondary outcome [3] 422689 0
Assess Anti-drug antibodies (ADAs) by collection of blood sample for assessment.
Timepoint [3] 422689 0
Day 1 (pre-dose), Day 15, Day 29, Day 85 post-dose, and Day169 post-dose.
Secondary outcome [4] 422690 0
Assess Cytokines assessments (IL-6, IFN-gamma, and TNF-alpha) by collection of blood sample for assessment.
Timepoint [4] 422690 0
Day 1 (pre-dose), Day 15, and Day 29 post-dose.

Eligibility
Key inclusion criteria
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 kg.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any clinically significant chronic 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 centigrade) 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 (seated or supine) at screening and Day -1.
5. Any liver function panel analyte value greater than upper limits of normal (ULN) which
includes aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin
(TBIL), and alkaline phosphatase (ALP) at screening and Day -1.
6. International normalized ratio (INR) above 1.2 × ULN at screening and Day -1.
7. Triplicate 12-lead electrocardiogram (ECG) with clinically significant abnormalities at
screening and Day -1, as determined by the clinical investigator.
8. History or clinical evidence of alcohol abuse, within the 12 months before screening.
9. History or clinical evidence of drug abuse, within the 12 months before screening.
10. Donated or lost >200 mL of blood within 30 days prior to screening.

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
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/07/2023
Actual
4/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 313963 0
Commercial sector/Industry
Name [1] 313963 0
Argo Biopharma Australia Pty Ltd
Country [1] 313963 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] 315834 0
None
Name [1] 315834 0
Address [1] 315834 0
Country [1] 315834 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313100 0
Bellberry Limited HREC
Ethics committee address [1] 313100 0
123 Glen Osmond Road Eastwood Adelaide South Australia 5063
Ethics committee country [1] 313100 0
Australia
Date submitted for ethics approval [1] 313100 0
07/06/2023
Approval date [1] 313100 0
03/07/2023
Ethics approval number [1] 313100 0

Summary
Brief summary
This study is investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single ascending dose of BW-20805 in healthy volunteers in 4 dose level cohorts. Approximately 32 men and women aged (more than equal to) 18 to (less than equal to) 60 years who fulfill the inclusion and exclusion criteria will be enrolled at one site in Australia. Eligible subjects will be admitted to the clinical research unit on Day -1, dosed on Day 1, discharged on Day 2 (24 hours post-dose), and return for outpatient visits through Week 24. Within each cohort, 8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20805 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion. Cohorts 1 to 4 and the control group will receive BW-20805 doses of 50mg, 150mg, 300mg, and 600mg, or placebo respectively.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127006 0
Dr Kristi McLendon
Address 127006 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 127006 0
Australia
Phone 127006 0
+61 07 3707 2720
Fax 127006 0
Email 127006 0
k.mclendon@nucleusnetwork.com.au
Contact person for public queries
Name 127007 0
Dr Xiafei Huang
Address 127007 0
Shanghai Argo Biopharmaceutical Co., Ltd, Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 127007 0
China
Phone 127007 0
+86 21 50360208
Fax 127007 0
Email 127007 0
xiafei.huang@argobiopharma.com
Contact person for scientific queries
Name 127008 0
Dr Xiafei Huang
Address 127008 0
Shanghai Argo Biopharmaceutical Co., Ltd, Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 127008 0
China
Phone 127008 0
+86 21 50360208
Fax 127008 0
Email 127008 0
xiafei.huang@argobiopharma.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.