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Trial registered on ANZCTR


Registration number
ACTRN12623001200673
Ethics application status
Approved
Date submitted
27/10/2023
Date registered
21/11/2023
Date last updated
10/11/2024
Date data sharing statement initially provided
21/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety of BW-20829 in subjects with elevated lipoprotein(a)
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered BW-20829 in subjects with elevated lipoprotein(a)
Secondary ID [1] 310778 0
BW-20829-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Elevated lipoprotein(a) 331743 0
Condition category
Condition code
Cardiovascular 328493 328493 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BW-20829 or placebo(sodium chloride injection, 0.9% w/v)
5 cohort doses (with up to 3 optional cohorts may be added):
8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20829 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion. Cohorts 1 to 5 will receive BW-20829 doses of 15, 50, 150, 300, and 600mg, or placebo respectively.
Maximum of additional 4 participants in a 3:1 ratio for PD assessment will be enrolled if deemed necessary.
Dose escalation will be based on the SRC’s assessment. For each cohort, all data (safety, tolerability, and trailing plasma PK and PD data) for a minimum of 6 evaluable subjects through to Day 8, as well as cumulative data from evaluable subjects across previous cohorts, will be reviewed by the SRC prior to dose escalation.
Participant will be admitted to the Phase 1 Clinical Trial Facility on Day -1 to take a 24-hour confinement and single dose of study drug will be administered by site staff on Day 1 to ensure adherence to the intervention. Individual patient records of subjects will be reviewed by monitor for intervention adherence.
The duration of administration: single dose
BW-20829 or placebo will be subcutaneously administered by registered nurse at Phase 1 clinical trial site.
The used and/or partially used vials can be disposed of per local practice. If the used and/or partially used vials cannot be disposed of at site, they will be returned, along with the unused vials, to the sponsor or its agent after receipt of written authorization from Sponsor.
For 3 optional cohorts:
• one optional cohort may be up to the 900 mg dose, especially if needed for TQT study,
• one optional cohort is at a dose below 15 mg, as this low dose will strengthen model prediction for Ph2&3.
• one optional cohort is to make one dose larger, and may not be needed. Will be informed by emerging data. It will depend on the variability of response of individual participants and if additional data will improve modeling prediction for Ph2&3.
The dose escalation for optional cohort like 900mg will be based on the SRC’s assessment and still need the sentinel safety assessment.
Other optional cohort(s) to assess doses the same or lower than those already administered to participants and approved by the SRC will not require SRC review. Optional cohorts at same or lower doses than already administered will not require sentinel dosing, be randomized 3:1.
Intervention code [1] 327184 0
Treatment: Drugs
Comparator / control treatment
Placebo
Sodium chloride injection (0.9% w/v) will be administered via subcutaneous injection.

Placebo Comparator: Placebo - Subject will be administered a single dose of placebo in the double-blind
Control group
Placebo

Outcomes
Primary outcome [1] 336310 0
To assess the safety and tolerability of single dose of BW-20829 in subjects with elevated lipoprotein(a) (Lp(a)) levels.
Assessment method [1] 336310 0
To be assessed by monitoring- . - Adverse events (AEs) and serious adverse events (SAEs) : be coded using the latest version of Medical Dictionary for Regulatory Activities (MedDRA). - Clinical laboratory findings (Hematology, clinical Chemistry, Coagulation and urinalysis): blood and urine sample collection and analysis - Vital sign measurements of systolic/diastolic blood pressure, Heart rate, body temperature and respiratory rate. The systolic/diastolic blood pressure and heart rate using the electronic blood pressure monitor, body temperature will be test by thermometer, respiratory rate will be observed and measured by study nurses. - 12-lead Electrocardiogram (ECG) - Physical examination findings -Toxicity grading will be based on: Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007).
Timepoint [1] 336310 0
The primary timepoint with window (days) for each visit are specified for Adverse events (AEs) and serious adverse events (SAEs): On day1, day 2, day 3, day 8, day 15(±2days), day 30(±2days), day45(±2days), day60(±2days), day90(±5days), day135(±5days), day180(±5days), day225(±7days), day270(±7days), day315(±7days), day 365(±7days) post-dose(End of Study/EOS) or early termination (ET). The primary timepoint with window (days) for each visit are specified for laboratory test: On screening(day-28 to day-1), day -1, day1, day 2, day 3, day 8, day 15(±2days), day 30(±2days), day45(±2days), day60(±2days), day90(±5days), day135(±5days), day180(±5days), day225(±7days), day270(±7days), day315(±7days), day 365(±7days) post-dose(EOS) or early termination (ET). The primary timepoint with window (days) for each visit are specified for Vital Signs: On screening(day-28 to day-1), day-1 and day 1 vital signs will be measured pre-dose and at 1-, 4-, and 8-hour post-dose. Once daily on day 2, day 3, day 8, day 15(±2days), day 30(±2days), day45(±2days), day60(±2days), day90(±5days), day135(±5days), day180(±5days), day225(±7days), day270(±7days), day315(±7days), day 365(±7days) post-dose(EOS) or early termination (ET). The primary timepoint with window (days) for each visit are specified for ECG: On screening(day-28 to day-1), day -1, day 1-2 will be measured by 24-hour Holter at pre-dose (-30, -20, -10 min), and at 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose, day 3, day 8, day 30(±2days), day 90(±5days), day 180(±5days), day 365(±7days) post-dose(EOS) or early termination (ET). The primary timepoint with window (days) for each visit are specified for Physical examination: On screening(day-28 to day-1), day -1, day1, day 2, day 3, day 8, day 15(±2days), day 30(±2days), day45(±2days), day60(±2days), day90(±5days), day135(±5days), day225(±7days), day270(±7days), day315(±7days) and day 365(±7days) post-dose(EOS). All above timepoints throughout this field are anchored relative to the participant.
Secondary outcome [1] 427819 0
Pharmacokinetic parameters and metabolites (if any)
Assessment method [1] 427819 0
Pharmacokinetics of BW-20829 will be derived using non-compartmental methods using Phoenix® WinNonlin® Version 8.3 or higher (Certara, LP Princeton, New Jersey, United States of America [USA]) and/or Statistical Analysis Software (SAS)® Version 9.4 or higher (SAS Institute, Inc., Cary, North Carolina, USA). The actual PK sampling times will be captured in the eCRF. Actual elapsed time from dosing will be used for the final PK parameter calculations. The pharmacokinetic parameters are as below: Cmax(Maximum concentration obtained directly from the observed concentration versus time data), Tmax(Time to Cmax), t1/2(Terminal elimination half-life), AUC0-48(Area under the serum concentration-time curve from time zero to 48 hours, calculated by linear up/log down trapezoidal summation), AUC0-inf (Area under the serum concentration-time curve from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation.) Additional PK parameters (plasma and urine) may be calculated if deemed appropriate.
Timepoint [1] 427819 0
Blood samples collected within 1 hour pre-dose and at 0.5(±5 mins), 1(± 10 mins), 2(± 10 mins), 4(± 15 mins), 8(± 30 mins), 12(± 30 mins), 18(± 1 hr), 24(± 1 hr), 48(±2 hrs), 168hours(±5 hrs) post-dose. Urine samples collected at pre dose, 0-4 hours, 4-12 hours and 12-24 hours intervals.
Secondary outcome [2] 427852 0
Pharmacodynamics parameter: serum (concentration) levels of lipoprotein(a)(Lp(a))
Assessment method [2] 427852 0
The serum (concentration) levels of lipoprotein(a) (Lp(a)) changes (including percent change) from baseline will be assessed as the pharmacodynamics parameter which using a molar assay at central lab. The pharmacodynamics parameter-Lp(a) serum analysis will be performed based on the PD Analysis Set, which is defined as all subjects in the SAS who have at least 1 non-missing pharmacodynamic assessment . The serum (concentration) levels of Lp(a) will be summarized at each visit.
Timepoint [2] 427852 0
Lp(a) test: On screening, day -1, day 1, day 3, day 8, day 15(± 2 days), day 30(± 2 days), day45(± 2 days), day60(± 2 days), Day90(± 5days), day135(± 5days), day180(± 5days), day225(± 7days), day270(± 7days), day315(± 7days), day 365(± 7days) post-dose (EOS) or early termination (ET). All above timepoints throughout this field are anchored relative to the participant.

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 65 years old, inclusive, at the time of informed consent.
3. Lp(a) >=50 mg/dL (125 nmol/L).
4. Body mass index >=18 and <=35 kg/m2 with body weight >50 kg.
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, can participate if they are using highly effective methods of contraception from 28 days prior to dosing until 12 weeks following administration of the study drug.
6. Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception from 28 days prior to dosing until 12 weeks following administration of the study drug.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any uncontrolled or serious disease, or any medical or surgical condition including evidence of unstable cardiovascular disease, and other serious medical or psychiatric illness/condition.
2. Any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease.
3. Any clinically significant acute condition such as fever (>38°c) or acute respiratory illness within 7 days of study drug administration.
4. Clinical laboratory findings outside of range are deemed clinically significant by the investigator at screening or Day -1.
5. 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 investigator).

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)
Unblinded pharmacy personnel at site assigns treatment to an eligible participant according to the randomization number and randomization schedule. Blinded site staff assign a randomization number to an eligible participant in a sequential order.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
Suspended
Date of first participant enrolment
Anticipated
15/12/2023
Actual
15/12/2023
Date of last participant enrolment
Anticipated
Actual
9/10/2024
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
52
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 315009 0
Commercial sector/Industry
Name [1] 315009 0
Argo Biopharma Australia Pty Ltd
Country [1] 315009 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Argo Biopharma Australia Pty Ltd
Country
Australia
Secondary sponsor category [1] 317031 0
None
Name [1] 317031 0
Country [1] 317031 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313980 0
Bellberry Limited HREC
Ethics committee address [1] 313980 0
Ethics committee country [1] 313980 0
Australia
Date submitted for ethics approval [1] 313980 0
11/10/2023
Approval date [1] 313980 0
09/11/2023
Ethics approval number [1] 313980 0

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 130006 0
Prof Gerald Watts
Address 130006 0
Linear Clinical Research, 1st Floor, B-Block, Hospital Avenue Nedlands WA 6009
Country 130006 0
Australia
Phone 130006 0
+61 415 698 140
Fax 130006 0
Email 130006 0
gerald.watts@uwa.edu.au
Contact person for public queries
Name 130007 0
Cindy Hua
Address 130007 0
Shanghai Argo Biopharmaceutical Co., Ltd, Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 130007 0
China
Phone 130007 0
+86 21 50360208
Fax 130007 0
Email 130007 0
zhi.hua@argobiopharma.com
Contact person for scientific queries
Name 130008 0
Alice Chang
Address 130008 0
Shanghai Argo Biopharmaceutical Co., Ltd, Floor 4, 581 Shenkuo Road, Shanghai, 201210, China
Country 130008 0
China
Phone 130008 0
+86 21 50360208
Fax 130008 0
Email 130008 0
zhuo.chang@argobiopharma.com

Data sharing statement
Will the study consider sharing individual participant data?
No


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.