Coronary Artery Disease, Lipidemia, Plaque, Atherosclerotic
Conditions
Brief summary
This placebo-controlled, double-blind, randomized, Phase 3 study is being conducted in adult participants with high-risk atherosclerotic cardiovascular disease (ASCVD) who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg + ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics, evaluated using cardiovascular computed tomography angiography (CCTA).
Interventions
Active treatment
OTHERPlacebo
Baseline lipid modifying therapy
Sponsors
NewAmsterdam Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind set-up; post randomization LDL values are not provided to sites (alert triggers are programmed for urgent follow-up)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fasting serum LDL-C ≥70 mg/dL (≥1.81 mmol/L) * Evaluable non-calcified plaque of at least 75 mm3 in the major epicardial coronary arteries * BMI 18-40, inclusive * Max tolerated lipid modifying therapy * Estimated glomerular filtration rate ≥40 mL/min/1.73 m2
Exclusion criteria
* HbA1c ≥10.0% (≥0.100 hemoglobin fraction) or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening * Contraindications for CCTA * History of coronary artery bypass graft * Active liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| • To evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg fixed dose combination (FDC) daily on total non-calcified coronary atherosclerotic plaque volume (NCPV) at 18 months. | 18 months | Total plaque comparison measured by CCTA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change from baseline to 18 months in total NCPV in all major epicardial coronary arteries, as measured by CCTA, in participants treated with obicetrapib 10 mg + ezetimibe 10 mg FDC therapy compared with placebo. | 18 Months | Total change in NCPV as measured by CCTA |
| Percent change from baseline to 18 months in LDL-C in participants treated with obicetrapib 10 mg + ezetimibe 10 mg FDC therapy compared to placebo. | 18 Months | Change in LDL-C levels measured by central lab |
| Percent change from baseline to 18 months in non-calcified coronary atherosclerotic plaque volume in the most diseased coronary segment (NCPVMD), as measured by CCTA, in participants treated with FDC therapy vs placebo | 18 Months | Percent change in plaque volume in most diseased coronary arteries measured by CCTA |
| Absolute change from baseline to 18 months in NCPVMD, as measured by CCTA, in participants treated with obicetrapib 10 mg + ezetimibe 10 mg FDC therapy compared with placebo. | 18 Months | Absolute change in plaque volume in most diseased coronary arteries measured by CCTA |
| Change in perivascular fat attenuation index (FAI), FAI score and its age- and gender specific centile in the principal epicardial coronary arteries as measured by CCTA in participants treated with FDC therapy compared with placebo. | 18 Months | Changes in coronary arterial fat composition measured by CCTA |
Countries
United States
Outcome results
None listed