Bempedoic acid/ezetimibe/high-intensity statin in patients without cardiovascular events

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Europe GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-06-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Europe GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Therapy, Efficacy

To evaluate the effectiveness of the triple therapy in reducing plaque burden.

Secondary objectives 11

1. To assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.
2. To evaluate the potential impact of the triple therapy on total plaque volume (TPV) regression, non-calcified PV regression, and low attenuation PV regression.
3. To evaluate the potential impact of the triple therapy on coronary calcification.
4. To investigate the relationship between LDL-C levels, and PB and non-calcified PB after triple therapy.
5. To evaluate the effectiveness of the triple therapy in reducing TPV.
6. To assess the proportion of participants exhibiting regression in TPV with triple therapy.
7. To assess changes in non-invasive coronary flow reserve.
8. To evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
9. To assess the potential impact of the triple therapy on measures of liver health.
10. To monitor and assess adverse events (AEs) under triple treatment.
11. To determine the rate and reasons for treatment discontinuation among trial participants receiving triple therapy.

Conditions and MedDRA coding

Coronary atherosclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥22 years
2. Having provided informed consent for participation in this trial
3. Lipid-lowering treatment-naïve
4. Presence of extensive coronary atherosclerosis meeting all of the criteria below: - Unequivocal atherosclerosis in ≥5 American Heart Association (AHA) coronary segments18 (corresponding to a risk equivalent of obstructive coronary artery disease) and coronary artery disease – reporting and data system (CAD-RADS)19 category 1, 2, or 3 - Not expected to be a candidate for revascularisation during the duration of the trial Note: Suspected obstructive coronary artery disease on PCD-CTA that was deemed non-obstructive during subsequent invasive coronary angiography (preferably assessed with invasive coronary physiology testing, e.g., fractional flow reserve), does not exclude patients from participating in the trial. - Untreated LDL-C ≥2.6 mmol/L and ≤4.5 mmol/L (where a diet without pharmacological treatment is considered ‘untreated')
5. Able to provide informed consent

Exclusion criteria 22

1. Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
2. Myopathy or other known contraindication for BA, EZE, atorvastatin, and/or rosuvastatin. A participant with a contraindication for atorvastatin, can be assigned to triple therapy with rosuvastatin, and vice versa.
3. Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
4. History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG])
5. Significant stenosis in the left main artery (≥50%) or proximal LAD artery (≥70%), or 3-vessel coronary artery disease (≥70% stenosis in major branches), clinically indicated for revascularisation
6. Known significant liver disease (e.g., positive hepatitis B or hepatitis C serology) or significant hepatic dysfunction (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >3 x upper limit of normal [ULN])
7. Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
8. Known estimated glomerular filtration rate (eGFR) <40 mL/min/1.73m² and/or receiving dialysis
9. Active malignancy (not including non-melanoma skin cancer)
10. Pregnant or breastfeeding
11. Body mass index (BMI) >35 kg/m2
12. Anticipated life expectancy <52 weeks at the discretion of the local investigator
13. Requiring emergent procedures or having any evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, severe congestive heart failure (New York Heart Association [NYHA] III or IV), or acute pulmonary oedema
14. Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
15. Complex congenital heart disease
16. Known or suspected severe valvular heart disease or valvular heart disease anticipated to require intervention within 52 weeks at the discretion of the local investigator
17. Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
18. Intracoronary stents
19. Prior pacemaker, internal defibrillator, or abandoned lead implantation
20. Prosthetic heart valves
21. Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
22. Use of any experimental or investigational drug within 40 days or 5 half-lives prior to Screening (whichever is longer), or parallel participation in another interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualised change in percentage plaque burden (Δ%PB) at End of Treatment (EoT)

Secondary endpoints 11

1. Annualised change in normalised non-calcified PV at EoT (in mm3).
2. Percentage of participants with regression in normalised TPV, normalised non-calcified PV, and normalised low attenuation PV at EoT (i.e., ΔPV and Δnon-calcified PV, and Δlow-attenuation PV).
3. Change in the absolute Agatston coronary artery calcium (CAC) score at EoT.
4. Relationship between the annualised change in LDL-C and the Δ%PB and Δ% non-calcified PB at EoT, as visualised by locally estimated scatterplot smoothing (LOESS) plot.
5. Annualised ΔTPV (in mm3) at EoT.
6. Percentage of participants with regression in TPV (i.e., negative ΔTPV) at EoT.
7. • Absolute annualised change in fractional flow reserve derived from computed tomography (FFRCT) of the vessel with the lowest FFR at Baseline. • Absolute annualised change in FFRCT of the average of 3 main epicardial coronary arteries (left anterior descending artery [LAD], circumflex artery [Cx], right coronary artery [RCA]).
8. Mean absolute changes in atherosclerosis-related biomarkers after 3 and 6 months and at EoT: total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides, lipoprotein (a) (Lp(a)), apolipoprotein B (apoB), and high-sensitive C reactive protein (hs-CRP).
9. Annualised changes in Framingham steatosis index (FSI) and fibrosis-4 (Fib-4)
10. Cumulative incidence of AEs under triple therapy during the trial.
11. The rate of treatment discontinuation and the reasons for treatment discontinuation during the trial.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Europe GmbH

Sponsor organisation

Daiichi Sankyo Europe GmbH

Address

Zielstattstrasse 48, Thalk.Obersendl.-Forsten-Fuerstenr.-Solln Thalk.Obersendl.-Forsten-Fuerstenr.-Solln

City

Munich

Postcode

81379

Country

Germany

Scientific contact point

Organisation

Daiichi Sankyo Europe GmbH

Contact name

Katharina Wenz-Pöschl

Public contact point

Organisation

Daiichi Sankyo Europe GmbH

Contact name

Bettina Steffens

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications