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

Beijing Inno Medicine

Status and phase: Begins enrollment this month; Phase 2

Conditions: Coronary Artery Disease; Atherosclerosis

Treatments: Drug: YN001/Placebo 40mg; Drug: YN001/Placebo 20mg; Drug: YN001/Placebo 0mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07521007

IND 157167 (Registry Identifier)

YN001-203

Details and patient eligibility

About

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.

Full 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).

Enrollment: 456 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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456 participants in 3 patient groups, including a placebo group

Dose 1 YN001/Placebo 40mg

Experimental group

Description:

Dose 1 YN001/Placobo 40mg will be administrated intravenously weekly

Treatment:

Drug: YN001/Placebo 40mg

Dose 2 YN001/Placebo 20mg

Experimental group

Description:

Dose 2 YN001/Placebo 20mg will be administrated intravenously weekly

Treatment:

Drug: YN001/Placebo 20mg

Dose 3 YN001/Placebo 0mg

Placebo Comparator group

Description:

Dose 3 YN001/Placebo 0mg will be administrated intravenously weekly

Treatment:

Drug: YN001/Placebo 0mg