Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001429741
Ethics application status
Approved
Date submitted
27/10/2022
Date registered
8/11/2022
Date last updated
30/05/2024
Date data sharing statement initially provided
8/11/2022
Date results information initially provided
30/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate BW-00112 in Adult Subjects
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered BW-00112 in Adult Subjects
Secondary ID [1] 308253 0
BW-00112-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Elevated Low-density lipoprotein cholesterol 328038 0
Condition category
Condition code
Metabolic and Endocrine 325095 325095 0 0
Metabolic disorders
Diet and Nutrition 325168 325168 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BW-00112
4 Cohorts: 50mg, 150mg, 300mg and 600mg
The duration of administration: single dose
BW-00112 will be administered via subcutaneous injection by registered nurse
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.
Intervention code [1] 324714 0
Treatment: Drugs
Comparator / control treatment
Placebo
Sodium chloride injection (0.9% w/v) will be administered via subcutaneous injection

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

Outcomes
Primary outcome [1] 332906 0
The primary outcomes are the safety and tolerability of BW-00112 will be assessed by determining the incidence and severity of adverse effects and changes in the laboratory parameters. The adverse events and changes in laboratory will be assessed by triplicate 12-lead ECG (heart rate, PR interval, QRS interval, QT and QTc interval), physical examination (includes, at a minimum skin, cardiovascular, respiratory, gastrointestinal and neurological systems), vital signs assessed by vital signs monitor (vital signs monitor can simultaneously monitor blood pressure, heart rate, respiratory rate and temperature), collection of blood sample for chemistry and hematology, serology ( HIV, HBV and HCV) , coagulation and collection of urine sample for urinalysis. Adverse effects will be coded using the latest version of MedDRA, summaries will be based on treatment emergent adverse events and will be evaluated and documented using Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007). The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. Those values or changes in values that are identified as being clinically significant will be flagged. Laboratory abnormalities of special interest, such as liver function tests will be summarized.
Timepoint [1] 332906 0
Day -1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day85 post-dose
Secondary outcome [1] 415074 0
Pharmacokinetic parameters analysis:
1. Maximum observed plasma concentration (Cmax): Up to 48 hours post-dose.
2. Time to maximum plasma concentration (Tmax): Up to 48 hours post-dose.
3. Area under the plasma concentration versus time curve from zero to 48 hours (AUC0-48).
4. Area under the plasma concentration versus time curve from zero to infinity (AUC0-inf).
5. Urine concentration up to 24 hours post-dose.
Timepoint [1] 415074 0
Blood samples collected at 0, 0.5, 1, 2, 4, 8, 12, 24 hrs and day 3 and 8 post-dose.
Urine samples collected at 0, 0-4, 4-12, 12-24 hrs post-dose
Secondary outcome [2] 415075 0
Change from baseline in serum angiopoietin-like protein 3
Timepoint [2] 415075 0
screening visit, Day -1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day85 post-dose
Secondary outcome [3] 415076 0
Change from baseline in serum fasting Triglycerides
Timepoint [3] 415076 0
screening visit, Day -1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day85 post-dose
Secondary outcome [4] 415443 0
Change from baseline in serum fasting high-density lipoprotein cholesterol
Timepoint [4] 415443 0
screening visit, Day -1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day85 post-dose
Secondary outcome [5] 415444 0
The incidence of serum anti-BW-00112 antibodies (ADAs) post-dose.
Timepoint [5] 415444 0
Day 1( 0 and 4 hrs post-dose), Day 15 and Day 29 post-dose
Secondary outcome [6] 415503 0
Change from baseline in serum fasting Low-density lipoprotein cholesterol
Timepoint [6] 415503 0
screening visit, Day -1, Day1, Day2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day85 post-dose
Secondary outcome [7] 415504 0
Change from baseline in serum fasting non-Low-density lipoprotein cholesterol
Timepoint [7] 415504 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose
Secondary outcome [8] 415505 0
Change from baseline in serum fasting lipoprotein (a)
Timepoint [8] 415505 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose
Secondary outcome [9] 415506 0
Change from baseline in serum fasting apolipoprotein B
Timepoint [9] 415506 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose
Secondary outcome [10] 415507 0
Change from baseline in serum fasting total cholesterol
Timepoint [10] 415507 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose
Secondary outcome [11] 415508 0
Change from baseline in serum fasting very low-density lipoprotein cholesterol
Timepoint [11] 415508 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose
Secondary outcome [12] 415509 0
Change from baseline in serum fasting apolipoprotein A1
Timepoint [12] 415509 0
screening visit, Day -1, Day 1, Day 2, Day 3, Day 8, Day 15, Day 22, Day 29,Day 43, Day 57 and Day 85 post-dose

Eligibility
Key inclusion criteria
1. All subjects are required to have elevated fasting Low-density lipoprotein cholesterol > = 100 mg/dL [2.69 mmol/L] and 100 mg/dL [1.13 mmol/L] < = Triglycerides (fasting) < 500 mg/dL [5.65 mmol/L] and have not been treated with lipid-lowering medicines in the past 3 month.
2. On a usual diet for at least 4 weeks prior to screening with no plans to significantly alter diet or weight over course of study.
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 clinically significant abnormality in laboratory parameters which in the judgment of the Investigator might compromise the safety of the subject or integrity of the study, interfere with the subject participation in the trial or compromise the trial objectives.
2. Any liver function panel analyte value > 1.5 x upper limits of normal reference range which includes Aspartate transaminase, Alanine transaminase, Total Bilirubin (for subjects with Gilbert’s Syndrome, total bilirubin < = 3.0 × upper limits of normal is allowed if direct bilirubin < = 50%), Alkaline Phosphatase, and gamma-glutamyl transferase at Screening.
3. International normalized ratio above 1.2 x upper limits of normal reference range reference range (as per the local laboratory reference range) at screening.
4. Calculated creatinine clearance < = 60 mL/min (Cockcroft-Gault equation).
5. History or presence of cardiovascular disease.
6. History or presence of Type 1 or type 2 diabetes mellitus at 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
Completed
Date of first participant enrolment
Anticipated
16/01/2023
Actual
31/01/2023
Date of last participant enrolment
Anticipated
Actual
2/06/2023
Date of last data collection
Anticipated
Actual
14/11/2023
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 312509 0
Commercial sector/Industry
Name [1] 312509 0
ARGO BIOPHARMA AUSTRALIA PTY LTD
Country [1] 312509 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ARGO BIOPHARMA AUSTRALIA PTY LTD
Address
Level 5, 63 Pirie Street, Adelaide, SA, 5023
Country
Australia
Secondary sponsor category [1] 314098 0
None
Name [1] 314098 0
Address [1] 314098 0
Country [1] 314098 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311845 0
Bellberry Limited
Ethics committee address [1] 311845 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 311845 0
Australia
Date submitted for ethics approval [1] 311845 0
16/11/2022
Approval date [1] 311845 0
19/12/2022
Ethics approval number [1] 311845 0

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled, single ascending dose study of BW-00112 when administered subcutaneously to subjects. Approximately 32 male and female subjects with elevated Low-density lipoprotein cholesterol , aged 18 to 65 years who fulfill the inclusion and exclusion criteria will be enrolled at 2 to 3 sites 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) after completing the 24-hour post-dose follow-up assessments, and return for outpatient visits through Day 85. There will be 4 separate and sequential dose cohorts. The population in Cohorts 1 to 4 (50mg, 150mg, 300mg and 600mg) will include subjects with fasting Low-density lipoprotein cholesterol levels > = 100 mg/dL and 100 mg/dL < = Triglycerides (fasting) < 500 mg/dL who are not on a lipid-lowering therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122574 0
Dr Emir Redzepagic
Address 122574 0
CMAX Clinical Research Pty Ltd, Level 5, 21-24 North Terrace, Adelaide SA 5000
Country 122574 0
Australia
Phone 122574 0
+61 413 231 264
Fax 122574 0
Email 122574 0
Emir.Redzepagic@cmax.com.au
Contact person for public queries
Name 122575 0
Mr Ty Burton
Address 122575 0
ARGO BIOPHARMA AUSTRALIA PTY LTD, Level 5, 63 Pirie Street,Adelaide SA 5000
Country 122575 0
Australia
Phone 122575 0
+61 08 83727900
Fax 122575 0
Email 122575 0
tburton@adel.bentleys.com.au
Contact person for scientific queries
Name 122576 0
Mr Ty Burton
Address 122576 0
ARGO BIOPHARMA AUSTRALIA PTY LTD, Level 5, 63 Pirie Street,Adelaide SA 5000
Country 122576 0
Australia
Phone 122576 0
+61 08 83727900
Fax 122576 0
Email 122576 0
tburton@adel.bentleys.com.au

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.