Intravascular Imaging Study of the Effect of Inclisiran on Plaque in Patients With Acute Myocardial Infarction (V-ACCELERATE)

A Multi-Center, Randomized, Open-label, Parallel, Controlled Phase Ⅳ Clinical Trial to Evaluate the Effect of Inclisiran on Coronary Atherosclerotic Plaque in Patients With Acute Myocardial Infarction and Elevated Low-density Lipoprotein Cholesterol

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Plaque, Atherosclerotic
• Intervention / Treatment: Drug: atorvastatin; Procedure: IVUS/OCT; Drug: inclisiran

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 318
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inclisiran and atorvastatin; Inclisiran 284mg SC (at D1,D90,D270)+ 20mg atorvastatin PO	Drug: atorvastatin; 20mg atorvastatin PO; Procedure: IVUS/OCT; performed the IVUS/OCT at baseline and Day 360; Drug: inclisiran; Inclisiran 284mg SC
Active Comparator: atorvastatin; 20mg atorvastatin PO	Drug: atorvastatin; 20mg atorvastatin PO; Procedure: IVUS/OCT; performed the IVUS/OCT at baseline and Day 360

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in percent atheroma volume (PAV)	Change in PAV assessed by intravascular ultrasound (IVUS) from baseline to Day 360.	Up to 360 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in minimum fibrous cap thickness (FCT)	Change in minimum FCT as determined by optical coherence tomography (OCT) from baseline to Day 360	Up to 360 days
Change in mean minimum FCT of all images	Change in mean minimum fibrous cap thickness (FCT) of all images as determined by OCT from baseline to Day 360.	360 days
Change in normalized total atheroma volume (NTAV)	Change in NTAV as determined by intravascular ultrasound (IVUS) from baseline to Day 360	Up to 360 days
Proportion of participants with progression, regression, or no change in PAV	Proportion of participants with progression, regression, or no change in percent atheroma volume (PAV) at Day 360	Up to 360 days
Change in LDL-C	Change in low-density lipoprotein cholesterol (LDL-C)	Baseline, Day 30, Day 150 and Day 360
Change in TC	Change in total cholesterol (TC).	Baseline, Day 30, Day 150 and Day 360
Change in HDL-C	Change in high-density lipoprotein cholesterol (HDL-C).	Baseline, Day 30, Day 150 and Day 360
Change in non-HDL-C	Change in non-high-density lipoprotein cholesterol (non-HDL-C).	Baseline, Day 30, Day 150 and Day 360
Change in ApoB	Change in apolipoprotein B (ApoB).	Baseline, Day 30, Day 150 and Day 360
Change in ApoA1	Change in apolipoprotein A1 (ApoA1).	Baseline, Day 30, Day 150 and Day 360
Change in Lp(a)	Change in lipoprotein (a) (Lp(a))	Baseline, Day 30, Day 150 and Day 360
Change in TG	Change in triglycerides (TG)	Baseline, Day 30, Day 150 and Day 360
Proportion of participants with LDL-C target attainment	Proportion of participants with LDL-C target attainment at Day 30, Day 150, and Day 360	Day 30, Day 150 and Day 360

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 23, 2024
• Primary Completion (Estimated): June 24, 2026
• Study Completion (Estimated): June 24, 2026

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PCI; Acute myocardial infarction,; OCT,; Atherosclerotic plaque,; Inclisiran,; IVUS,
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Myocardial Infarction; Infarction; Plaque, Atherosclerotic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: CKJX839A1CN04 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No