A Clinical Study of IMC-001 for Injection in Improving Atherosclerotic Plaque Stability in Patients With Acute Coronary Syndrome.

A Two-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Investigator-Initiated Trial (IIT) Evaluating the Safety and Preliminary Efficacy of IMC-001 for Injection in Improving Atherosclerotic Plaque Stability in Patients With Acute Coronary Syndrome.

A two-center, randomized, double-blind, placebo-controlled, dose-escalation IIT clinical study evaluating the safety and preliminary efficacy of injectable IMC-001 in improving atherosclerotic plaque stability in patients with acute coronary syndrome. The plan is to conduct 2 dose groups, with 9 subjects enrolled in each group, including 6 in the treatment group and 3 in the control group. The treatment group will receive IMC-001 along with optimal drug therapy, with a total of 12 subjects included, while the control group will receive a placebo along with optimal drug therapy, with a total of 6 subjects included.

Inclusion Criteria:

1. Fully comprehend the purpose, characteristics, methodology, and potential adverse reactions of this study; voluntarily participate in the research and sign an informed consent form prior to any related assessments;

2. Male or female subjects aged ≥18 years and ≤75 years;

3. Clinically diagnosed with acute coronary syndrome (ACS) (including acute myocardial infarction or unstable angina) and meeting the following criteria:

   ① Patients with ≥30% and <70% stenosis in the target vessel as demonstrated by coronary angiography or coronary CTA;

   ② At least one plaque exhibiting detectable low attenuation (coronary CTA -30 HU to 30 HU), with calcified volume constituting <50% of total plaque volume;

   ③ High-sensitivity C-reactive protein (hsCRP) ≥ 1.0 mg/L;

4. Patients must receive guideline-directed standard treatment for coronary artery disease;

5. Women of childbearing potential or men (unless their partner is infertile) must agree to use medically approved contraception from screening until 6 months after the last dose; Male subjects must not donate sperm, and female subjects must not donate eggs for at least 6 months after signing the informed consent form and until 6 months after the last dose.

Exclusion Criteria:

1. Participation in any drug or medical device clinical trial within one month prior to screening.

2. Previous treatment with coronary artery bypass grafting (CABG), left ventricular assist device (LVAD) implantation, heart transplantation, surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR), or any planned procedure for these treatments during the study period.

3. New York Heart Association (NYHA) functional class III or IV, or a known recent left ventricular ejection fraction (LVEF) < 40% (as determined by left ventricular angiography, radionuclide ventriculography, or echocardiography).

4. Uncontrolled arrhythmia within 3 months prior to screening, defined as recurrent, symptomatic, and refractory to medical therapy, such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate and paroxysmal supraventricular tachycardia, or a family history of long QT syndrome.

5. Evidence of active or suspected malignancy within 3 years prior to screening (excluding only carcinoma in situ or basal/squamous cell skin cancer treated with curative therapy); life expectancy less than 1 year.

6. Any major surgery within 3 months prior to screening or planned major surgery during the study period;

7. Presence or suspected ongoing severe infection within 8 weeks prior to first dosing (defined as requiring hospitalisation or intravenous anti-infective therapy), chronic or recurrent bacterial, fungal, or viral infections requiring medical intervention, including syphilis, human immunodeficiency virus (HIV) infection, active hepatitis B or C infection history;

8. Presence of severe hepatic dysfunction, defined as: any alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 3 times the upper limit of normal (ULN) at final screening assessment.

9. Moderate to severe renal impairment, defined as: estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m²at screening (calculated using the 2021 CKD-EPI formula; see Appendix 4), or serum creatinine > 1.5 × ULN.

10. Presence of any type of autoimmune disease; current or planned systemic anti-inflammatory therapy, such as immunomodulatory agents and chemotherapeutic agents.

11. Individuals who have donated blood or experienced blood loss

    ≥400 mL within 3 months prior to dosing, have a history of severe spontaneous bleeding, or have received blood transfusions or blood products. Abnormal laboratory parameters within 7 days without transfusion, including but not limited to: white blood cell count below the lower limit of normal, neutrophil count <1.5×109/L, haemoglobin <100 g/L, platelet count ≤100×109 /L, total bilirubin >1.5×ULN, International Normalised Ratio (INR) >2×ULN, or activated partial thromboplastin time (APTT) >2×ULN.

12. Known prior allergy to macromolecular protein preparations/monoclonal antibodies, known allergy to the investigational medicinal product or its excipients or similar drugs, prior treatment with IMC-001.

13. Existence of contraindications for CCTA examination and history of iodine contrast agent allergy, etc.

14. Screening CCTA reveals moderate to severe calcification (coronary artery calcium score [Agatston score] ≥ 300) or tortuosity in target vessels, judged by the investigator to compromise study assessment.

15. Receipt of any type of vaccination within one month prior to screening, or planned vaccination during the study treatment period.

16. History of substance abuse (including illicit drug use) and/or alcohol abuse within 6 months prior to screening; subjects with alcohol abuse defined as consuming 14 units of alcohol weekly: 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine.

17. Pregnant or lactating women; those with a positive pregnancy test during the screening period.

18. Any other disease or condition deemed by the investigator to make the subject unsuitable for participation in this study, in addition to those listed above.