atherosclerosis Atherosclerotic Cardiovascular Disease
Conditions
Interventions
Approximately 9000 eligible participants will be randomized in a 1:1 ratio to
the following treatment groups:
- Study Medicine group: One 10 mg study medicine tablet QD
or
- Placebo group: One placebo tablet QD.
Sponsors
NewAmsterdam Pharma BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female and >=18 years of age at Screening (Visit 1); 2. Have a history of ASCVD, defined by at least 1 of the following conditions: - Coronary artery disease - Cerebrovascular disease - Peripheral arterial disease 3. Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid lowering diet and other lifestyle modifications, defined as follows: - A statin at a maximally tolerated stable dose; - Ezetimibe for at least 8 weeks with or without a maximally tolerated statin prior to Screening (Visit 1); - Bempedoic acid for at least 8 weeks in combination with a maximally tolerated statin prior to Screening (Visit 1); - A PCSK9-targeted therapy alone or in combination with other lipidmodifying therapy for at least 4 stable doses prior to Screening (Visit 1); - At least 70% of the participants enrolled into this study must be taking HISs. Documentation in the eCRF of the reason why a participant is unable to take HISs is required. HISs include the following: o Atorvastatin 40 and 80 mg; and o Rosuvastatin 20 and 40 mg 4. Have a fasting serum LDL-C at Screening (Visit 1) as follows: - Have a fasting serum LDL-C >=70 mg/dL to 3 and 150 mg/dL (>1.7 mmol/L); and/or - Fasting high density lipoprotein cholesterol =100 mg/dL. 5. Have fasting TG =30 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening (Visit 1). Other protocol-defined criteria apply.
Exclusion criteria
Exclusion criteria: 1. Have current or any previous history of New York Heart Associationclass III or IV HF or left ventricular ejection fraction =160 mmHg or diastolic blood pressure >=100 mmHg prior to Randomization, taken as the average of triplicate measurements. One triplicate retest will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the participant may be randomized; 5. Have a formal diagnosis of homozygous familial hypercholesterolemia; 6. Have active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal (ULN); or total bilirubin >2 × ULN at Screening (Visit 1); 7. Have an HbA1c >=10.0% or a fasting glucose >=270 mg/dL at Screening (Visit 1); 8. Have a thyroid-stimulating hormone >1.5 × ULN at Screening (Visit 1); 9. Have a creatine kinase >3 ×ULN at Screening (Visit 1); 10. Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1). Other protocol-defined criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is the time from Randomization to the first confirmed occurrence of any component of the composite endpoint, including the following: • CV death; • Non-fatal MI; • Non-fatal stroke; or • Non-elective coronary revascularization. SAFETY • AEs and events of special interest (ESIs); • Vital signs (including blood pressure); • Electrocardiograms; and • Clinical laboratory assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints, in hierarchical order, include the following: • The time from Randomization until the first confirmed occurrence of a composite of CV death, non-fatal MI, or non-fatal stroke; • The time from Randomization until the first confirmed occurrence of a composite of all-cause mortality, non-fatal MI, non-fatal stroke, or non- elective coronary revascularization; • A total event analysis, defined as the number of CV death events, and first and subsequent/recurrent events of non-fatal MIs, non-fatal strokes, and non-elective coronary revascularization from Randomization until the EOS Visit; • The time from Randomization until the first confirmed occurrence of non-fatal MI; • The time from Randomization until the first confirmed occurrence of non-elective coronary revascularization; • The time from Randomization until the first confirmed occurrence of CV death; • The time from Randomization until the first confirmed occurrence non-fatal stroke; • The time from Randomization until the confirmed occurrence of allcause mortality; • The time from Randomization until the first confirmed occurrence of NODM; • Percent change in LDL-C from Baseline to Day 365 and to the EOT Visit; • Percent change in non-HDL-C from Baseline to Day 365 and to the EOT Visit; • Percent change in ApoB from Baseline to Day 365; and • Percent change in HbA1c in participants with diabetes mellitus and HbA1c >=7% at Baseline, from Baseline to Day 365 and to the EOT Visit. The exploratory efficacy endpoints include the time from Randomization until the first confirmed occurrence of the following: • Hospitalization for unstable angina and/or chest pain; • Hospitalization for HF; and • TIA | — |
Countries
Netherlands
Outcome results
None listed