A study to assess the safety and tolerability of BRB-002 in adults with established atherosclerosis
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
Bitterroot Bio Australia Pty Ltd
52 participants
May 27, 2025
Interventional
Conditions
Summary
This is a double blind, placebo-controlled multiple dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneous BRB-002 in patients with established atherosclerosis, Up to approximately 52 participants with established atherosclerosis will be randomised into this study. The study will be conducted with a multiple dose phase (Part A) and a cohort expansion phase (Part B). Part A cohorts will contain up to 8 participants each with 6 participants receiving BRB-002 and 2 participants receiving placebo. Part B will be a dose expansion phase where a further 20 participants tested with the optimal dosing regimen determined during Part A. For each cohort, a Safety Review Committee (SRC) will review all emerging safety, tolerability, PK and PD data. The next planned cohort will be initiated only after it is confirmed by the SRC that the latest cohort dose was safe and tolerated.
Eligibility
Inclusion Criteria15
- Written informed consent must be obtained before any study assessment is performed.
- Adults between 45 and 80 years of age (inclusive) at time of signing of informed consent.
- Minimum and maximum body weights of 50.0 and 120.0 kg, inclusive.
- 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
- Willing and able to undergo 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT and CCTA scans.
- Able to communicate well with the Investigator, to understand and comply with the requirements of the study.
- Maximum target-to-background ratio >= 1.6 (either right or left carotid artery) on 18F-FDG-PET/CT, signifying active inflammation.
Exclusion Criteria12
- 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.
- History of hypersensitivity to any of the IPs or excipients or to drugs of similar chemical classes
- Donation or loss of 400 ml or more of blood within 8 weeks prior to IP administration, or longer if required by local regulation.
- Significant illness which has not resolved within 2 weeks prior to initial dosing.
- 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
- Inadequately controlled hypertension (systolic blood pressure >=160 mm Hg or diastolic blood pressure >=100 mm Hg) at screening
- Diabetics taking injectable insulin or an HbA1c > 8% at Screening.
- Participants with permanent atrial fibrillation
- History of heart failure defined as most recent left ventricular ejection fraction <30% or New York Heart Association class III or IV at screening.
- Renal impairment with creatinine clearance < 40 ml/min (using Cockcroft-Gault equation), or history of kidney transplant, or history of contrast nephropathy.
- Pregnant or nursing (lactating) women
- Women of child-bearing potential defined as all women physiologically capable of becoming pregnant.
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Interventions
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.
Locations(1)
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ACTRN12625000273482