Clinical trial NCT06700720: YN001-004 in Patients With Coronary Atherosclerosis in Australia
Official title: A Phase Ⅱa Clinical Study to Evaluate the Efficacy and Safety of YN001 in Patients With Coronary Atherosclerosis in Australia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Coronary Artery Disease
Coronary Atherosclerotic Disease
Keywords: Coronary Atherosclerosis
Plaque regression
Lead sponsor: Beijing Inno Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-11-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 12 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 (6 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).

Eligibility criteria: 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. Severe coronary calcification.
6. Multi-vessel severe disease.
7. Recent acute ST-segment elevation myocardial infarction (STEMI) occurred within 2 weeks prior to randomization.
8. 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.
9. Prior treatment with CABG, heart transplantation, SAVR/TAVR, etc., or CABG, heart transplantation, SAVR/TAVR, etc., is required or planned during the study.
10. PCI performed within 4 weeks prior to randomization or PCI is required or planned during study treatment.
11. New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction (LVEF) \<40%.
12. Recent clinically evident stroke occurred within 6 months prior to randomization (except for TIA).
13. Evidence of major diseases that not recovered within 2 weeks prior to randomization, or major surgery is expected during the study.
14. 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).
15. Systolic blood pressure of ≥150 mmHg at final screening despite antihypertensive therapy.
16. 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.
17. Presence of renal insufficiency.
18. Poorly controlled (defined by HbA1c \> 9%) type 2 diabetes mellitus.
19. 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).
20. 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.

Primary outcomes:
measure: Changes in coronary plaque characteristics (volume and composition)
timeFrame: From baseline to Week 13
Secondary outcomes:
measure: Change in mean of mean carotid IMT
timeFrame: From baseline to Week 13
measure: Change in mean of mean carotid IMT
timeFrame: From baseline to Week 5
measure: Change in mean of mean carotid IMT
timeFrame: From baseline to Week 9
measure: Change in mean peri-coronary Fat attenuation index (FAI)
timeFrame: From baseline to Week 13
measure: The safety profile of YN001
timeFrame: From baseline to Week 15
measure: Plasma concentration of total and free drug
timeFrame: From Week 1 to Week 13
measure: Population pharmacokinetics (PK)
timeFrame: From Week 1 to Week 13
Other outcomes:
measure: Immunogenicity（ADA） analysis
timeFrame: From Week 1 to Week 13
measure: Immunogenicity （APA）analysis
timeFrame: From screening to Week 13
measure: Exploratory dose-response analysis of plaque volume
timeFrame: From Week 1 to Week 13
measure: Exploratory dose-response analysis of AEs
timeFrame: From Week 1 to Week 13
Locations:
city: Canberra
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Albury
country: Australia
facility: Albury Wodonga Private Hospital
state: New South Wales
city: Milton
country: Australia
facility: Core Research Group Pty Ltd
state: Queesland
city: Melbourne
country: Australia
facility: Altona Clinical Research
state: Victoria
city: Melbourne
country: Australia
facility: Peninsula Heart Centre
state: Victoria
Study officials:
affiliation: Beijing Inno Medicine Co., Ltd.
name: Teresa Chen, PhD
role: STUDY_DIRECTOR
References: