Study Description
This study is to evaluate the effect of Inclisiran on coronary atherosclerosis using
intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in patients with
acute myocardial infarction and elevated low-density lipoprotein cholesterol (LDL-C). This study will be a multi-center, randomized, parallel-group, open-label, phase 4 study.
Participants will be approximately 318 Chinese adults diagnosed with new-onset
STEMI/NSTEMI and elevated LDL-C (LDL-C > 1.8 mmol/L if on stable dose of statin (with or
without ezetimibe) for ≥ 4 weeks; LDL-C > 2.6 mmol/L if not on stable dose of statin
(with or without ezetimibe) for ≥ 4 weeks). Participants will be 1:1 randomized to
investigational group (Inclisiran 284mg + 20mg atorvastatin) or control group (20mg
atorvastatin) for 360 days. Participants and investigator will be unblinded to the
identity of the treatment from the time of randomization. Independent Review Committee
(IRC) staff performing the study assessments (IVUS and OCT analysis) will be blinded to
the identity of the treatment from the time of randomization until final database lock.
Interventions
atorvastatin
inclisiran
IVUS/OCT
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.
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