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

Overview

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 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).

Interventions

• 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.
• 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.
• Drug Evolocumab
  Evolocumab 140 mg will be administered subcutaneously every 2 weeks.

Primary outcome measures

• Changes in coronary plaque characteristics (volume and composition) [Time frame: From baseline to Week 13]

Secondary outcome measures (7)

• Change in mean of mean carotid IMT [Time frame: From baseline to Week 13]
• Change in mean of mean carotid IMT [Time frame: From baseline to Week 5]
• Change in mean of mean carotid IMT [Time frame: From baseline to Week 9]
• Change in mean peri-coronary Fat attenuation index (FAI) [Time frame: From baseline to Week 13]
• The safety profile of YN001 [Time frame: From baseline to Week 15]
• Plasma concentration of total and free drug [Time frame: From Week 1 to Week 13]
• Population pharmacokinetics (PK) [Time frame: From Week 1 to Week 13]

Eligibility criteria

Inclusion criteria

• Fully understand the purposes, features, and methods of the study, and sign the ICF before performing any assessment.
• Male or female Australia patients between 18 and 75 years.
• Patients diagnosed with coronary atherosclerosis, and at least 1 vessel with diameter stenosis determined by coronary computed tomography angiography (CTA).
• 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.
• Willing and able to comply with the requirements of protocol to the best of the patient'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.
• Contraindication for coronary CTA (e.g., known history of anaphylactic contrast reactions).
• Multi-vessel severe disease.
• Recent acute ST-segment elevation myocardial infarction (STEMI) occurred within 2 weeks prior to randomization.
• 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.
• Prior treatment with CABG, heart transplantation, SAVR/TAVR, etc., or CABG, heart transplantation, SAVR/TAVR, etc., is required or planned during the study.
• PCI performed within 4 weeks prior to randomization or PCI is required or planned during study treatment.
• New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction (LVEF) <40%.
• Recent clinically evident stroke occurred within 6 months prior to randomization (except for TIA).
• Presenting with history of myopathy/myalgia, or susceptible to myopathy/rhabdomyolysis.
• Known inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding within 6 months prior to randomization.
• Evidence of major diseases that not recovered within 2 weeks prior to randomization, or major surgery is expected during the study.
• 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).
• Presence of any type of autoimmune disease.
• Allergy to multiple food or drugs or known sensitivity to any components to be administered during dosing
• Life expectancy is less than 1 year.
• Systolic blood pressure of ≥150 mmHg at final screening despite antihypertensive therapy.
• Known familial hypercholesterolemia
• Triglycerides≥400 mg/dl (4.5 mmol/l) at final screening.
• 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.
• Presence of renal insufficiency.
• Untreated or inadequately treated hypothyroidism defined by thyroid stimulating hormone (TSH) > 1.5 times ULN at final screening.
• Poorly controlled (defined by HbA1c > 9%) 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).
• Current smoker who has smoked an average of≥5 cigarettes (or equivalent) per day over the preceding year.
• 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.

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

Single blind

Primary purpose

Treatment

Study locations

Australia · 7 centers

• Canberra Hospital — Canberra
• Albury Wodonga Private Hospital — Albury
• Sunshine Coast University Private Hospital — Birtinya
• Core Research Group Pty Ltd — Milton
• Altona Clinical Research — Melbourne
• Peninsula Heart Centre — Melbourne
• John Flynn Private Hospital — Tugun

Identifiers

NCT: NCT06700720 · YN001-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗