A Phase 2b Clinical Trial of YN001 in Adults With Coronary Atherosclerosis

Official title

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

Overview

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.

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).

Interventions

• 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.
• 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.
• 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.

Primary outcome measures

• Relative change from baseline in coronary NCPV at Week 13 [Time frame: Baseline to Week 13]

Secondary outcome measures (12)

• Absolute change from baseline in carotid intima-media thickness (IMT) at Week 13 [Time frame: From baseline to Week 13]
• Absolute change from baseline in carotid intima-media thickness (IMT) at Week 9 [Time frame: From baseline to Week 9]
• Relative change from baseline in carotid intima-media thickness (IMT) at Week 13 [Time frame: From baseline to Week 13]
• Relative change in the maximum thickness and area of carotid plaque at Week 9, and Week 13 [Time frame: From baseline to Week 9 and Week 13]
• Relative change in coronary Percent Atheroma Volume (PAV) at Week 13 [Time frame: From baseline to Week 13]
• Relative change in coronary Low Attenuation Plaque Volume(LAPV) at Week 13 [Time frame: From baseline to week 13]
• Relative changes in coronary NCPV, PAV, TAV, and LAPV from baseline at 48 week [Time frame: From baseline to week 48]
• Absolute change in coronary NCPV at week 13 and week 48 [Time frame: From baseline to week 13 and week 48]
• Time to First Occurrence of Any Component of the Major Adverse Cardiac Event (MACE) [Time frame: From randomization to Week 96]
• The safety profile of YN001 [Time frame: From baseline to Week 13]
• Immunogenicity (ADA) analysis [Time frame: From baseline to Week 13]
• Immunogenicity (APA) analysis [Time frame: From baseline to Week 17]

Eligibility criteria

Inclusion criteria

• 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.
• Male or female participants between 18 and 80 years (inclusive, at the time of signing the ICF).
• 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:

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

• Prior treatment with other investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to randomization.
• Previously received YN001.
• Any type of vaccination within 4 weeks prior to randomization, or any planned vaccination during the study treatment period
• Contraindication for CCTA
• 3 major epicardial coronary arteries with ≥ 70% or left main ≥50% stenosis.
• Acute MI that occurred within 4 weeks prior to randomization.
• PCI performed within 2 weeks prior to randomization or PCI is required or planned during study treatment based on clinical indication for revascularization.
• Clinically evident stroke or transient ischemic attack (TIA) within 6 months prior to randomization.
• Relapse and highly symptomatic arrhythmia uncontrolled by drugs within the past 3 months.
• 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.
• New York Heart Association class III or IV or last known left ventricular ejection fraction (LVEF) was <40%.
• Carotid endarterectomy or stenting, peripheral arterial revascularization, or abdominal aortic aneurysm repair within 4 weeks prior to randomization.
• History of myopathy or myositis, or susceptibility to myopathy/rhabdomyolysis (e.g., family history of hereditary myopathy, etc.).
• History of severe myalgia attributed to statin therapy or other significant concern about statin side effects.
• Known gastrointestinal ulcers, inflammatory bowel disease, or gastrointestinal/rectal bleeding within 6 months prior to randomization.
• 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.
• 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).
• Presence of any type of autoimmune disease.
• Allergy to multiple foods or drugs or known sensitivity to any components to be administered during dosing.
• Life expectancy is less than 1 year.
• Systolic blood pressure of ≥ 160 mmHg at final screening despite antihypertensive therapy.
• Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at final screening.
• LDL-C > 100 mg/dL (2.6 mmol/L) at final screening.
• 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.
• Presence of renal dysfunction, defined by eGFR < 45 ml/min/1.73m2.
• Untreated or inadequately treated hypothyroidism.
• Poorly controlled Type 2 diabetes mellitus.
• 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).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 13 centers

• Anhui Provincial Hospital — Hefei
• Anzhen Hospital — Beijing
• Beijing Jishuitan Hospital — Beijing
• Fujian Medical University Union Hospital — Fuzhou
• The First Affiliated Hospital of Harbin Medical University — Harbin
• Zhongnan Hospital of Wuhan University — Wuhan
• The First Hospital of Jilin University — Changchun
• The People's Hospital of Liaoning Province — Shenyang
• … and 5 more centers

United States · 12 centers

• Heart Center Research, LLC — Huntsville
• Clinical Trials Research — Lincoln
• Stanford University School of Medicine — Stanford
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center — Torrance
• Excel Medical Clinical Trials dba Flourish Research - Boca Raton — Boca Raton
• HCA Florida Heart Institute — Petersburg
• Southern Illinois University School of Medicine — Springfield
• Midwest Heart & Vascular Specialists — Overland Park
• … and 4 more centers

Australia · 2 centers

• Cannopy Clinical Research — Penrith
• Canopy Clinical Research — Altona N.

Canada · 1 center

• North York Diagnostic and Cardiac Center — North York

Identifiers

NCT: NCT07521007 · YN001-203 · IND 157167

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗