YN001-004 in Patients With Coronary Atherosclerosis in Australia

A Phase Ⅱa Clinical Study to Evaluate the Efficacy and Safety of YN001 in Patients With Coronary Atherosclerosis in Australia

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)

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Coronary Atherosclerotic Disease
• Intervention / Treatment: Drug: Evolocumab; Drug: Dose 2 YN001; Drug: Dose 1 YN001

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).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jean Zhang; Phone Number: 861082599080; Email: zhangjing@innovmedicine.com

Study Locations

• Australia
  • Tugun, Australia
    • Not yet recruiting
    • John Flynn Private Hospital
    • Contact: Ashok Gangasandra Basavaraj /PI, Doctor; Phone Number: 07 5598 0882; Email: ashokgangasandra@gmail.com
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia
      • Recruiting
      • Canberra Hospital
      • Contact: Walter Abhayaratna, PhD
  • New South Wales
    • Albury, New South Wales, Australia, 1125
      • Recruiting
      • Albury Wodonga Private Hospital
      • Contact: Fiore
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • Sunshine Coast University Private Hospital
      • Contact: Thackwray
  • Queesland
    • Milton, Queesland, Australia
      • Withdrawn
      • Core Research Group Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3199
      • Recruiting
      • Peninsula Heart Centre
      • Contact: Szto
    • Melbourne, Victoria, Australia, 3025
      • Recruiting
      • Altona Clinical Research
      • Contact: Walsh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 2 treatment arm; Dose 2 YN001 will be administrated intravenously weekly.	Drug: Evolocumab; Evolocumab 140 mg will be administered subcutaneously every 2 weeks.; Other Names: Repatha®; Drug: Dose 2 YN001; Dose 2 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Experimental: Dose 1 treatment arm; Dose 1 YN001 will be administrated intravenously weekly.	Drug: Evolocumab; Evolocumab 140 mg will be administered subcutaneously every 2 weeks.; Other Names: Repatha®; Drug: Dose 1 YN001; Dose 1 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From baseline to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	From baseline to Week 13
The safety profile of YN001	Incidence of Adverse events (AEs)/Serious adverse events (SAEs)	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	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.	From Week 1 to Week 13

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity（ADA） analysis	The proportion of patients who develop anti-drug antibodies (ADA) following drug administration.	From Week 1 to Week 13
Immunogenicity （APA）analysis	The proportion of patients with pre-exsiting anti-PEG antibodies (APA), treatment emergent APA or treatment boosted APA following drug administration.	From screening to Week 13
Exploratory dose-response analysis of plaque volume	Exploratory dose-response analysis will be performed by comparing the difference of coronary plaque volume changing between 2 different dose levels	From Week 1 to Week 13
Exploratory dose-response analysis of AEs	Exploratory dose-response analysis will be performed by comparing the difference of incidence of AEs between 2 different dose levels	From Week 1 to Week 13

Collaborators and Investigators

• Sponsor: Beijing Inno Medicine Co., Ltd.
• Investigators: Study Director: Teresa Chen, PhD, Beijing Inno Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Coronary Atherosclerosis; Plaque regression
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; PCSK9 Inhibitors; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antimetabolites; Serine Proteinase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; evolocumab
• Other Study ID Numbers: YN001-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No