Intravascular Imaging Study of the Effect of Inclisiran on Plaque in Patients With Acute Myocardial Infarction

Launched by NOVARTIS PHARMACEUTICALS · Apr 15, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a medication called Inclisiran to see how it affects plaque buildup in the coronary arteries of patients who have recently had a heart attack, known as an acute myocardial infarction. The trial will use advanced imaging techniques to measure changes in the arteries after treatment with Inclisiran. The goal is to determine if this medication can help reduce the harmful cholesterol levels that contribute to plaque formation in the arteries.

To participate in this study, individuals must be between 18 and 75 years old and have experienced a heart attack within a specific time frame. They should also have certain levels of bad cholesterol (LDL-C) and at least one artery with a specific level of plaque. Participants can expect to undergo imaging tests to assess their heart health before and after treatment. It's important to note that those with certain heart conditions, previous heart surgeries, or specific health issues may not be eligible to join the study.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male or female ≥ 18 and ≤ 75 years of age.
• • 2. Acute myocardial infarction (STEMI ≤ 24h/NSTEMI ≤ 72h of onset of symptoms) with planned PCI.
• 3. At least 1 major, non-infarct-related coronary artery ("target vessel") meet all of the following criteria judged by the investigator:
• • 1) Presence of atherosclerotic plaque with ≥ 20% and ≤ 50% diameter stenosis by coronary angiography.
• 2) Target vessel deemed to be accessible to imaging catheters and suitable for intravascular imaging in the proximal (50 mm) segment ("target segment") 3) Target vessel is suitable for IVUS and OCT evaluation. 4) Not have undergone previous PCI within target vessel. 5) Not be a bypass graft or a bypassed native vessel. 4. Rapid LDL-C test value at screening period of:
• • 1. LDL-C \> 1.8 mmol/L if on stable dose of statin (with or without ezetimibe) for ≥ 4 weeks upon signing ICF.
• • 2. LDL-C \> 2.6 mmol/L if not on stable dose of statin (with or without ezetimibe) for ≥ 4 weeks upon signing ICF.
• • 5. Written informed consent must be obtained.
• Exclusion Criteria:
• • 1. Familial hypercholesterolemia or secondary hypercholesterolemia.
• • 2. Clinically instable AMI (hemodynamic or electrical instability).
• • 3. Left main disease, defined as ≥ 50% diameter stenosis of the left main coronary artery by coronary angiography.
• • 4. Three-vessel disease, defined as ≥ 70% diameter stenosis of 3 major epicardial coronary vessels or in major branches of these arteries by coronary angiography.
• • 5. Have a plan for interventional procedure within 12 months after signing ICF.
• • 6. Known intolerance to Atorvastatin OR known statin intolerance.
• • 7. Patients already on high-intensity statin including atorvastatin 40 or 80 mg or rosuvastatin 20 mg upon signing ICF.
• • 8. Patients not suitable for IVUS/OCT evaluation (e.g., significant calcification , etc) judged by the investigator.
• • 9. Patients qualify for coronary artery bypass surgery at screening and history of coronary artery bypass surgery.
• 10. Cardiac disorders:
• • 1) Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening; 2) Pacemaker or ICD in situ; and/or 3) Uncontrolled severe hypertension with systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to randomization despite antihypertensive therapy.
• • 11. Rapid lipid test triglyceride (TG) level \> 400mg/dL (4.5 mmol/L) at screening.
• • 12. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), \> 3x the upper limit of normal (ULN), or total bilirubin \> 2x ULN before the randomization.
• • 13. Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2(Calculated according to the modified MDRD equation).
• • 14. Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.
• • 15. Previous (within 90 days before randomization), current or planned treatment with a PCSK9 monoclonal antibody (mAb).
• • 16. Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy 2 years prior to randomization.
• • 17. Participation in another investigational device or drug study currently, or within 5 half-live (if drug) or 30 days whichever is longer, prior to randomization.
• • 18. History of hypersensitivity to any study drug or its excipients. 19. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study and/or put the participant at significant risk according to investigator's judgment.
• • 20. Pregnant or nursing (lactating) women. 21. Women of child-bearing potential, unless they are using effective methods of contraception during study treatment.
• • 22. Any conditions that according to the investigator could interfere with the conduct of the study.