The goal of this clinical trial is to determine the clinical effect of orticumab treatment on inflammation in study participants with prior myocardial infarction who have elevated coronary inflammation based on CCTA. The main question it aims to answer is:
Clinical effects of orticumab treatment on inflammation of the coronary artery parameters measured with CCTA
Researchers will compare the effects with placebo group after 6 months of treatment
Participants will Keep the planned study visit appointments Provide complete information about medical and medical history Speak to the study doctor before changing any of non-study treatments, including starting new medications, receiving any vaccinations, or setting out to join any other clinical studies
Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization and must adhere to the schedules of activities.
Participant must be >180 days after presumed type-1 myocardial infarction (i.e., due to plaque rupture or erosion, either STEMI or NSTEMI) without subsequent unstable or severe angina (Canadian Cardiovascular Society Class 3 or 4) at the time of enrollment. Participants who have undergone PCI are allowed.
Participant must be on a stable cardiovascular treatment regimen consistent with local treatment guidelines for post-AMI patients (such as maximally tolerated statin and/or PCSK9 inhibitor medication for LDL reduction, antiplatelet medication, and hypertension treatment).
A quantifiable Fat Attenuation Index (FAI) Score greater than or equal to the 50th centile (per reference standard) for their age group in at least two coronary arteries or
History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
Percutaneous coronary intervention or invasive diagnostic coronary angiogram planned after screening. Eligible participants who have an invasive diagnostic coronary angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.
History of or planned coronary artery bypass grafting.
Documented episode of post-MI pericarditis in the 3 months before enrollment.
Parallel
Orticumab
DrugOrticumab treatment for 24 weeks for post MI population
Placebo
DrugPlacebo for 24 weeks for the post MI population
Percent change from baseline of the mean Fat Attenuation Index (FAI) score for the 3 coronary arteries (RCA, LAD and LCX) for orticumab compared to placebo at 24 weeks
Analysis of the mean FAI score around the coronary arteries will be performed from baseline and 6-month Coronary Computed Tomography Angiography (CCTA) procedures. FAI-score is a standardized measurement of coronary inflammation for each coronary artery (adjusted for age, sex as well as technical, biological, and anatomical characteristics) to allow individualized interpretation of the degree of coronary inflammation. FAI-Score is given at a scale of 0-100 with arbitrary unit. A higher FAI-score indicates an increase coronary inflammation.
Change from baseline for coronary artery inflammation
Change from baseline for Fat Attenuation Index (FAI) parameters for orticumab compared to placebo after 24 weeks of treatment assessed by Coronary Computed Tomography Angiography (CCTA)
Change from baseline for CaRi-Heart score for orticumab compared to placebo at 24 weeks of treatment
CaRi-Heart Risk score represents the individualized patient risk of a fatal cardiac event at 8 years which incorporates the FAI score values into a prognostic model that includes information about CCTA-derived plaque metrics and clinical cardiovascular risk factors (diabetes, smoking, hypertension, hyperlipidemia).
Change in coronary artery plaque burden accessed by Coronary Computed Tomography Angiography (CCTA) at 24 weeks
Change in coronary artery plaque parameters for orticumab compared to placebo at 24 weeks of treatment assessed by CCTA
Change in radiotranscriptomic biomarkers of coronary inflammation as assessed by Coronary Computed Tomography Angiography (CCTA)
Change from baseline on radiotranscriptomic biomarkers of coronary inflammation (e.g. C19RS) as measured by CCTA compared to placebo to determine the effects of orticumab treatment on coronary inflammation
Number and percent of participants with treatment-emergent adverse events (TEAEs), and any serious adverse events
Incident of abnormal vital signs
Vital signs (including blood pressure and pulse rate) are measured and recorded at every visit to assess the safety and tolerability of orticumab in study participants. Incidence of abnormal vital signs will be recorded.
