Coronary Artery Disease, Coronary Atherosclerotic Disease
Conditions
Keywords
Coronary Atherosclerosis, Plaque regression
Brief summary
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)
Detailed description
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).
Interventions
DRUGEvolocumab
Evolocumab 140 mg will be administered subcutaneously every 2 weeks.
DRUGDose 1 YN001
Dose 1 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.
DRUGDose 2 YN001
Dose 2 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Sponsors
Beijing Inno Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Fully understand the purposes, features, and methods of the study, and sign the ICF before performing any assessment. 2. Male or female Australia patients between 18 and 75 years. 3. Patients diagnosed with coronary atherosclerosis, and at least 1 vessel with diameter stenosis determined by coronary computed tomography angiography (CTA). 4. Female patients must be non-pregnant and non-lactating, and females of childbearing potential (including a female partner of a male patient) must agree to use 1 effective contraception method from the screening period to 3 months after receiving their last dose of the study drug. In addition, male patients must be willing to refrain from sperm donation during this time. 5. Willing and able to comply with the requirements of protocol to the best of the patient's and investigator's knowledge.
Exclusion criteria
1. Prior treatment with other investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to randomization. 2. Previously received YN001. 3. Any type of vaccination within 4 weeks prior to randomization. 4. Contraindication for coronary CTA (e.g., known history of anaphylactic contrast reactions). 5. Multi-vessel severe disease. 6. Recent acute ST-segment elevation myocardial infarction (STEMI) occurred within 2 weeks prior to randomization. 7. Relapse and highly symptomatic arrhythmia uncontrolled by drugs within the past 3 months, such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate and paroxysmal supraventricular tachycardia. 8. Prior treatment with CABG, heart transplantation, SAVR/TAVR, etc., or CABG, heart transplantation, SAVR/TAVR, etc., is required or planned during the study. 9. PCI performed within 4 weeks prior to randomization or PCI is required or planned during study treatment. 10. New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction (LVEF) \<40%. 11. Recent clinically evident stroke occurred within 6 months prior to randomization (except for TIA). 12. Presenting with history of myopathy/myalgia, or susceptible to myopathy/rhabdomyolysis. 13. Known inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding within 6 months prior to randomization. 14. Evidence of major diseases that not recovered within 2 weeks prior to randomization, or major surgery is expected during the study. 15. Presenting with history of malignancy (except in patients who have been disease-free \>5 years; or whose only malignancy has been basal or squamous cell skin carcinoma). 16. Presence of any type of autoimmune disease. 17. Allergy to multiple food or drugs or known sensitivity to any components to be administered during dosing 18. Life expectancy is less than 1 year. 19. Systolic blood pressure of ≥150 mmHg at final screening despite antihypertensive therapy. 20. Known familial hypercholesterolemia 21. Triglycerides≥400 mg/dl (4.5 mmol/l) at final screening. 22. Active liver disease or hepatic dysfunction defined by any of ALT, AST, or total bilirubin \> 2 times upper limit of normal (ULN) at final screening. 23. Presence of renal insufficiency. 24. Untreated or inadequately treated hypothyroidism defined by thyroid stimulating hormone (TSH) \> 1.5 times ULN at final screening. 25. Poorly controlled (defined by HbA1c \> 9%) type 2 diabetes mellitus. 26. A positive hepatitis B surface antigen (HBsAg), or positive antibody against hepatitis C virus (anti-HCV) or human immunodeficiency virus (anti-HIV), or positive treponema pallidum antibody (TP-Ab). 27. Current smoker who has smoked an average of≥5 cigarettes (or equivalent) per day over the preceding year. 28. Presence of any other diseases or conditions (apart from those outlined above) that, in the opinion of the investigator, would make it unsuitable for the patient to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in coronary plaque characteristics (volume and composition) | From baseline to Week 13 | Evaluating YN001 on top of evolocumab therapy in changing coronary plaque volume assessed by coronary computed tomography angiography (CCTA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean of mean carotid IMT | From baseline to Week 13 | Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound. |
| Change in mean peri-coronary Fat attenuation index (FAI) | From baseline to Week 13 | Evaluating YN001 on top of evolocumab therapy in changing inflammation using the peri-coronary FAI value measured by quantitative CTA analysis. |
| The safety profile of YN001 | From baseline to Week 15 | Incidence of Adverse events (AEs)/Serious adverse events (SAEs) |
| Plasma concentration of total and free drug | From Week 1 to Week 13 | Plasma concentration of total and free drug at pre-dose (0 h) and at the end of infusion |
| Population pharmacokinetics (PK) | From Week 1 to Week 13 | Plasma PK parameter (AUC) and patient covariates of interest will be evaluated graphically and in the population PK model. |
Countries
Australia
Contacts
CONTACTJean Zhang
STUDY_DIRECTORTeresa Chen, PhD
Beijing Inno Medicine Co., Ltd.
Outcome results
None listed