A Phase 2b Clinical Trial of YN001 in Adults With Coronary Atherosclerosis (PURIFY-TIMI 81)

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-controlled Phase 2b Clinical Trial to Evaluate the Efficacy and Safety of YN001 in Adults With Coronary Atherosclerosis

This study is designed to evaluate the efficacy and safety of intravenously administered YN001 in patients diagnosed with coronary atherosclerosis, who are receiving background therapy for cardiovascular (CV) risk factors management.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Atherosclerosis
• Intervention / Treatment: Drug: YN001/Placebo 40mg; Drug: YN001/Placebo 20mg; Drug: YN001/Placebo 0mg

Detailed Description

This is a multinational, multicenter, randomized, parallel, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of intravenously administered YN001 compared with placebo in participants with coronary atherosclerosis who are receiving background therapy for CV risk factors management.

A total of 456 participants are expected to be enrolled. The study will consist of a maximum 12-week screening/Baseline period, followed by a 12-week blinded treatment period, a 30-day safety follow-up, and a long-term follow-up period through Week 96 (approximately 2 years after randomization).

• Study Type: Interventional
• Enrollment (Estimated): 456
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingmei Zhang, Master; Phone Number: 0086 010 82599080; Email: zhangjingmei@innovmedicine.com
• Study Contact Backup: Name: Kaiqi Zong, Master; Phone Number: 0086 010 82599080; Email: zongkaiqi@innovmedicine.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
      • Contact: Kangyu Chen, MD; Phone Number: 0086 18056005099; Email: ustccky@126.com
      • Principal Investigator: Kangyu Chen, MD
      • Sub-Investigator: Chao Gao, MD
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100035
      • Beijing Jishuitan Hospital
      • Principal Investigator: Wei Liu, MD
      • Contact: Qingwei Ji, MD; Phone Number: 0086 18376642655; Email: jqwl24@163.cou
      • Principal Investigator: Qingwei Ji, MD
    • Beijing, Beijing Municipality, China, 100029
      • Anzhen Hospital
      • Contact: Yuyang Liu, MD; Phone Number: 0086 010-64456488; Email: liuyy803803@163.com
      • Principal Investigator: Yuyang Liu, MD
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
      • Contact: Mingfang Ye, MD; Phone Number: 0086 13960818759; Email: xieheyemingfang@163.com
      • Principal Investigator: Mingfang Ye, MD
      • Sub-Investigator: Zhaoyang Chen, MD
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The First Affiliated Hospital of Harbin Medical University
      • Contact: Lu Fu, MD; Phone Number: 0086 137 9668 4968; Email: fuluyidayi@163.com
      • Principal Investigator: Lu Fu, MD
      • Principal Investigator: Yongtai Gong, MD
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital Of Wuhan University
      • Contact: Zhibing Lu, MD; Phone Number: 0086 15997405817; Email: luzhibing222@163.com
      • Principal Investigator: Zhibing Lu, MD
  • Jilin
    • Changchun, Jilin, China, 130033
      • The First Hospital of Jilin University
      • Principal Investigator: Qian Tong, MD
      • Contact: Qian Tong, MD; Phone Number: 0086 13074337289; Email: tongqian187@aliyun.com
  • Liaoning
    • Shenyang, Liaoning, China, 110015
      • The People's Hospital of Liaoning Province
      • Principal Investigator: Ying Liu, MD
      • Contact: Ying Liu, MD; Phone Number: 0086 13840065379; Email: liuyingwangli@126.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200001
      • Renji Hospital Shanghai Jiaotong University School of Medicine
      • Contact: Jun Bu, MD; Phone Number: 0086 13601958108; Email: pujun310@hotmail.com
      • Principal Investigator: Jun Bu, MD
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University-Zhongshan Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Yong He, MD; Phone Number: 0086 18980602038; Email: zznnyeah@163.com
      • Principal Investigator: Yong He, MD
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300211
      • The Second Hospital of Tianjin Medical University
      • Contact: Tong Liu, MD; Phone Number: 0086 13902183163; Email: liutongdoc@126.com
      • Principal Investigator: Tong Liu, MD
    • Tianjin, Tianjin Municipality, China, 300121
      • Tianjin People's Hospital
      • Principal Investigator: Zhuhua Yao, MD
      • Contact: Zhuhua Yao, MD; Phone Number: 0086 13902199877; Email: tjyzhpci@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Fully understands the purposes, features, and methods of the study and the possible adverse reactions, and is voluntarily willing to participate in the study, and signs the informed consent form (ICF) before performing any study-specific assessment.
2. Male or female participants between 18 and 80 years (inclusive, at the time of signing the ICF).
3. Participants must satisfy either of the following criteria:

1) Have clinically evident atherosclerotic CV disease (ASCVD) 2) Meet at least two of the following criteria at screening/baseline, as evidenced by:

1. A history of Type 2 diabetes requiring treatment with medication,
2. Aged > 55 years (women) or > 50 years (men),

3. 2 or more of the following atherosclerosis risk factors:

   • Current cigarette smoker
   • Hypertension

   • Estimated glomerular filtration rate (eGFR) 45 to 60 ml/min/1.73m2

     4. Known coronary atherosclerosis as evidenced through coronary angiography or CCTA. The following criteria must be met on the core lab CCTA interpretation for the patient to be enrolled: at least one epicardial coronary artery with a lumen stenosis of 25% to 69%, total coronary NCPV is at least 75 mm3, Detectable low-attenuation composition in one or more individual plaques.

     5. Female participants must be non-pregnant and non-lactating

     6. Willing and able to comply with the requirements of protocol to the best of the participant'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, or any planned vaccination during the study treatment period
4. Contraindication for CCTA
5. 3 major epicardial coronary arteries with ≥ 70% or left main ≥50% stenosis.
6. Acute MI that occurred within 4 weeks prior to randomization.
7. PCI performed within 2 weeks prior to randomization or PCI is required or planned during study treatment based on clinical indication for revascularization.
8. Clinically evident stroke or transient ischemic attack (TIA) within 6 months prior to randomization.
9. Relapse and highly symptomatic arrhythmia uncontrolled by drugs within the past 3 months.
10. Prior coronary artery bypass graft (CABG), aortic root surgery with coronary reimplantation, left ventricular assist device (LVAD) placement, surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR), or heart transplantation, or a plan to undergo these procedures (CABG, aortic root surgery with coronary reimplantation, LVAD placement, SAVR, TAVR, or heart transplantation) during the study.
11. New York Heart Association class III or IV or last known left ventricular ejection fraction (LVEF) was <40%.
12. Carotid endarterectomy or stenting, peripheral arterial revascularization, or abdominal aortic aneurysm repair within 4 weeks prior to randomization.
13. History of myopathy or myositis, or susceptibility to myopathy/rhabdomyolysis (e.g., family history of hereditary myopathy, etc.).
14. History of severe myalgia attributed to statin therapy or other significant concern about statin side effects.
15. Known gastrointestinal ulcers, inflammatory bowel disease, or gastrointestinal/rectal bleeding within 6 months prior to randomization.
16. Evidence of unresolved major diseases 2 weeks prior to randomization or planned major surgery during the study that, in the investigator's judgement, may interfere with the investigational product administration or trial assessments.
17. Presenting with history of malignancy (except in participants who have been disease-free >5 years; or whose only malignancy has been basal or squamous cell skin carcinoma).
18. Presence of any type of autoimmune disease.
19. Allergy to multiple foods or drugs or known sensitivity to any components to be administered during dosing.
20. Life expectancy is less than 1 year.
21. Systolic blood pressure of ≥ 160 mmHg at final screening despite antihypertensive therapy.
22. Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at final screening.
23. LDL-C > 100 mg/dL (2.6 mmol/L) at final screening.
24. Active liver disease or hepatic dysfunction defined by any of alanine aminotransaminase (ALT), aspartate aminotransferase (AST), > 3 times upper limit of normal (ULN), or total bilirubin > 2 times ULN at final screening.
25. Presence of renal dysfunction, defined by eGFR < 45 ml/min/1.73m2.
26. Untreated or inadequately treated hypothyroidism.
27. Poorly controlled Type 2 diabetes mellitus.
28. 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).
29. 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 participant to participate in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1 YN001/Placebo 40mg; Dose 1 YN001/Placobo 40mg will be administrated intravenously weekly	Drug: YN001/Placebo 40mg; Dose 1 YN001/Placebo 40mg will be administrated on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Experimental: Dose 2 YN001/Placebo 20mg; Dose 2 YN001/Placebo 20mg will be administrated intravenously weekly	Drug: YN001/Placebo 20mg; YN001/Placebo 20mg will be administrated on Day 1 of each week from Week 1 to Week 13, 13 times in total.
Placebo Comparator: Dose 3 YN001/Placebo 0mg; Dose 3 YN001/Placebo 0mg will be administrated intravenously weekly	Drug: YN001/Placebo 0mg; YN001/Placebo 0mg will be administrated 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
Relative change from baseline in coronary NCPV at Week 13	Relative change in coronary NCPV from baseline to Week 13 as determined by coronary computed tomography angiography (CCTA)	Baseline to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in carotid intima-media thickness (IMT) at Week 13	Absolute change in carotid IMT from baseline to Week 13 as determined by carotid ultrasound.	From baseline to Week 13
Absolute change from baseline in carotid intima-media thickness (IMT) at Week 9	Absolute change from baseline in carotid intima-media thickness (IMT) at Week 9	From baseline to Week 9
Relative change from baseline in carotid intima-media thickness (IMT) at Week 13	Relative change in carotid IMT from baseline to Week 13 as determined by carotid ultrasound	From baseline to Week 13
Relative change in the maximum thickness and area of carotid plaque at Week 9, and Week 13	Relative change in the maximum thickness and area of carotid plaque from baseline to Week 9, and Week 13 as determined by carotid ultrasound	From baseline to Week 9 and Week 13
Relative change in coronary Percent Atheroma Volume (PAV) at Week 13	Relative change in coronary Percent Atheroma Volume (PAV) from baseline to Week 13 as determined by CCTA	From baseline to Week 13
Relative change in coronary Low Attenuation Plaque Volume(LAPV) at Week 13	Relative change in coronary LAPV from baseline to Week 13 as determined by CCTA.	From baseline to week 13
Relative changes in coronary NCPV, PAV, TAV, and LAPV from baseline at 48 week	Relative changes in coronary NCPV, PAV, TAV, and LAPV from baseline to Week 48 as determined by CCTA	From baseline to week 48
Absolute change in coronary NCPV at week 13 and week 48	Absolute change in coronary NCPV from baseline to Week 13 and Week 48 as determined by CCTA	From baseline to week 13 and week 48
Time to First Occurrence of Any Component of the Major Adverse Cardiac Event (MACE)	Time to the first occurrence of the MACE, composite of CV death, myocardial infarction (MI), ischemic stroke, urgent coronary revascularization, or hospitalization for unstable angina	From randomization to Week 96
The safety profile of YN001	Incidence of treatment emergent adverse event (TEAE)/serious adverse event (SAE)/adverse event of special interest (AESI)	From baseline to Week 13
Immunogenicity (ADA) analysis	Incidence of anti-drug antibodies (ADA) formation	From baseline to Week 13
Immunogenicity (APA) analysis	Incidence of anti-PEG antibodies (APA) formation	From baseline to Week 17
YN001 concentrations analysis in plasma	Sparse blood samples will be collected, and these concentrations are intended to be pooled with other studies to develop/update pharmacometric models	From baseline to Week 13

Collaborators and Investigators

• Sponsor: Beijing Inno Medicine Co., Ltd.
• Collaborators: The TIMI Study Group
• Investigators: Study Director: Ying Chen, PhD, Beijing Inno Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Plaque regression; Plaque stabilization
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; Atherosclerosis
• Other Study ID Numbers: YN001-203; IND 157167 (Registry Identifier: Beijing Inno Medicine Co., Ltd.)

Drug and device information, study documents

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