Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000273482
Ethics application status
Approved
Date submitted
5/02/2025
Date registered
10/04/2025
Date last updated
24/08/2025
Date data sharing statement initially provided
10/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to assess the safety and tolerability of BRB-002 in adults with established atherosclerosis
Scientific title
A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous BRB-002 in Patients with Established Atherosclerosis
Secondary ID [1] 313350 0
BRB-002-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 335707 0
Condition category
Condition code
Cardiovascular 332274 332274 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 332275 332275 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BRB-002 is a recombinant fusion protein that is designed to potently block CD47.
Investigational Product BRB-002 or matching Placebo for subcutaneous (SC) injection.
Approximately 52 participants will be enrolled in the study.

Multiple doses of BRB-002 or matching placebo will be administered to study participants via subcutaneous (SC) injection by site staff. There will be up to four cohorts in Part A of the study with each cohort comprising of 6 participants receiving BRB-002 and 2 participants receiving placebo (total of approximately 8 participants per cohort).

The first Part A cohort will evaluate weekly doses ranging from weekly 0.1 mg/kg to 5 mg/kg which were evaluated during the prior Phase 1 study. For subsequent cohorts, a Safety Review Committee (SRC) will review available data and decide on the the dosing regimen for the next cohort. An adaptive design will be used that allows for modification of study dose levels based on previous cohort safety, tolerability and PK data. Dose levels for each subsequent cohort will be determined by the SRC.

Part B will be a dose expansion cohort with approximately a further 20 participants dosed at the optimal dose and frequency from Part A at a 1:1 randomisation to BRB-002 or placebo.

All participants will be monitored for 13 weeks during the treatment phase and a further 5 weeks during a follow-up phase.

Adherence to the intervention will be monitored by the study staff, CRO and Sponsor.
Intervention code [1] 329935 0
Treatment: Drugs
Comparator / control treatment
Matching placebo in single use vials. The placebo is a pH buffered salt solution with standard preservatives, but no active drug product.
Control group
Placebo

Outcomes
Primary outcome [1] 339843 0
Safety and tolerability of multiple dose SC administration of BRB-002
Timepoint [1] 339843 0
Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 44, Day 46, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85 (EOT), Day 86, Day 88, Day 92, Day 99, Day 106, Day 114 and Day 120 (EOS).
Primary outcome [2] 340743 0
Safety and tolerability of multiple dose SC administration of BRB-002
Timepoint [2] 340743 0
Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 50, Day 57, Day 64, Day 71 Day 78 and Day 85 (end of treatment).
Primary outcome [3] 340744 0
Safety and tolerability of multiple dose SC administration of BRB-002
Timepoint [3] 340744 0
Screening, Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 44, Day 46, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85 (EOT), Day 86, Day 88, Day 92, Day 99, Day 106, Day 113 and Day 120 (EOS).
Secondary outcome [1] 441623 0
Pharmacokinetics (PK) of BRB-002 by SC administration
Timepoint [1] 441623 0
Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 44, Day 46, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85 (EOT), Day 86, Day 88, Day 92, Day 106, and Day 120 (EOS).
Secondary outcome [2] 444980 0
Pharmacodynamics (PD) of BRB-002 by SC administration
Timepoint [2] 444980 0
Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 44, Day 46, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85 (EOT), Day 86, Day 88, Day 92, Day 106, and Day 120 (EOS).

Eligibility
Key inclusion criteria
1. Written informed consent must be obtained before any study assessment is performed.
2. Adults between 45 and 80 years of age (inclusive) at time of signing of informed consent.
3. Minimum and maximum body weights of 50.0 and 120.0 kg, inclusive.
4. Past history of myocardial infarction or transient ischemic attack or stroke at least 12 months before screening OR documented asymptomatic carotid artery stenosis greater than or equal to 50% OR at least 2 of the following:
• Age >= 65
• Hypertension
• Hyperlipidaemia
[If receiving lipid-lowering therapy, lipid lowering therapy must be unchanged for at least 12 weeks prior to screening]
• Current smoking including use of e-cigarettes.
• Non-insulin dependent diabetes mellitus
• High sensitivity C-reactive protein >= 2 mg/L at screening
• Peripheral arterial disease
5. Willing and able to undergo 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT and CCTA scans.
6. Able to communicate well with the Investigator, to understand and comply with the requirements of the study.
7. Maximum target-to-background ratio >= 1.6 (either right or left carotid artery) on 18F-FDG-PET/CT, signifying active inflammation.

Minimum age
45 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participation in another clinical study of another IP within 5 half-lives of enrolment, or within 30 days for small molecules or until the expected pharmacodynamic effect has returned to baseline for biologics, whichever is longer or longer if required by local regulations.
2. History of hypersensitivity to any of the IPs or excipients or to drugs of similar chemical classes
3. Donation or loss of 400 ml or more of blood within 8 weeks prior to IP administration, or longer if required by local regulation.
4. Significant illness which has not resolved within 2 weeks prior to initial dosing.
5. History of acute coronary syndrome, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, transient ischemic attack, stroke (any aetiology), or sudden cardiac arrest within 12 months prior to screening
6. Inadequately controlled hypertension (systolic blood pressure >=160 mm Hg or diastolic blood pressure >=100 mm Hg) at screening
7. Diabetics taking injectable insulin or an HbA1c > 8% at Screening.
8. Participants with permanent atrial fibrillation
9. History of heart failure defined as most recent left ventricular ejection fraction <30% or New York Heart Association class III or IV at screening.
10. Renal impairment with creatinine clearance < 40 ml/min (using Cockcroft-Gault equation), or history of kidney transplant, or history of contrast nephropathy.
11. Pregnant or nursing (lactating) women
12. Women of child-bearing potential defined as all women physiologically capable of becoming pregnant.

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)
Central randomisation by computer
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/04/2025
Actual
27/05/2025
Date of last participant enrolment
Anticipated
31/03/2026
Actual
Date of last data collection
Anticipated
29/07/2026
Actual
Sample size
Target
52
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 317796 0
Commercial sector/Industry
Name [1] 317796 0
Bitterroot Bio
Country [1] 317796 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Bitterroot Bio Australia Pty Ltd
Address
Country
United States of America
Secondary sponsor category [1] 320124 0
None
Name [1] 320124 0
Address [1] 320124 0
Country [1] 320124 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316480 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 316480 0
Ethics committee country [1] 316480 0
Australia
Date submitted for ethics approval [1] 316480 0
05/02/2025
Approval date [1] 316480 0
28/03/2025
Ethics approval number [1] 316480 0

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

Contacts
Principal investigator
Name 138026 0
Dr Sam Francis
Address 138026 0
Emeritus Research, Ground Floor/1096 Toorak Rd, Camberwell VIC 3124
Country 138026 0
Australia
Phone 138026 0
+61 3 9509 6166
Fax 138026 0
Email 138026 0
[email protected]
Contact person for public queries
Name 138027 0
Emily Dale
Address 138027 0
Bitterroot Bio Pty Ltd, Suite 220, 3160 Porter Drive, Palo Alto, CA 94304
Country 138027 0
United States of America
Phone 138027 0
+16504072004
Fax 138027 0
Email 138027 0
[email protected]
Contact person for scientific queries
Name 138028 0
Craig Basson, MD
Address 138028 0
Bitterroot Bio Pty Ltd, Suite 540, 75 Second Avenue, Needham, MA 02494, USA
Country 138028 0
United States of America
Phone 138028 0
+1 978 386 6480
Fax 138028 0
Email 138028 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: To protect participant privacy



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.