This study is to evaluate the efficacy and safety of intravenously administered YN001 in patients with coronary atherosclerosis in Australia. This study will be conducted in eligible participants with a diagnosis of coronary atherosclerosis, and at least 1 coronary artery is blocked determined by coronary computed tomography angiography (CCTA)
This is a multicenter, randomized, open label, parallel-group, proof of concept study. It is designed to determine if the study drug, called YN001, administered in addition to evolocumab can effectively reduce the total amount of plaque formed in the coronary artery as measured by CCTA from baseline to week 13. A total of 24 patients with coronary atherosclerosis are expected to be enrolled and will be randomly assigned in a 1:1 ratio to 1 of 2 YN001 treatment arms (12 patients per arm) with 2 different dose levels for 12 weeks. The study will be comprised of a maximum 41-day screening period (Day -42-Day -2), a baseline period (Day-1), a treatment and observation period (W1D1- W13D7), and a safety follow-up period (14 days post last dose).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
3
Dose 1 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Dose 2 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Evolocumab 140 mg will be administered subcutaneously every 2 weeks.
Canberra Hospital
Canberra, Australian Capital Territory, Australia
Albury Wodonga Private Hospital
Albury, New South Wales, Australia
Sunshine Coast University Private Hospital
Birtinya, Queensland, Australia
Altona Clinical Research
Melbourne, Victoria, Australia
Changes in coronary plaque characteristics (volume and composition)
Evaluating YN001 on top of evolocumab therapy in changing coronary plaque volume assessed by coronary computed tomography angiography (CCTA).
Time frame: From baseline to Week 13
Change in mean of mean carotid IMT
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound.
Time frame: From baseline to Week 13
Change in mean of mean carotid IMT
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound.
Time frame: From baseline to Week 5
Change in mean of mean carotid IMT
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound.
Time frame: From baseline to Week 9
Change in mean peri-coronary Fat attenuation index (FAI)
Evaluating YN001 on top of evolocumab therapy in changing inflammation using the peri-coronary FAI value measured by quantitative CTA analysis.
Time frame: From baseline to Week 13
The safety profile of YN001
Incidence of Adverse events (AEs)/Serious adverse events (SAEs)
Time frame: From baseline to Week 15
Plasma concentration of total and free drug
Plasma concentration of total and free drug at pre-dose (0 h) and at the end of infusion
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Peninsula Heart Centre
Melbourne, Victoria, Australia
John Flynn Private Hospital
Tugun, Australia
Time frame: From Week 1 to Week 13
Population pharmacokinetics (PK)
Plasma PK parameter (AUC) and patient covariates of interest will be evaluated graphically and in the population PK model.
Time frame: From Week 1 to Week 13