Effects of ziltivekimab on coronary atherosclerotic burden in patients with acute myocardial infarction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S, ECRI-trials B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 Feb 2026 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2024-520364-34-00

WHO UTN

U1111-1316-8221

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To demonstrate the superiority of ziltivekimab vs placebo once-monthly, added to standard of care (SOC) therapy, in inducing favorable effects on change in percent atheroma volume (PAV) in participants with acute myocardial infarction (AMI)

Secondary objectives 4

1. To demonstrate the superiority of ziltivekimab vs placebo once-monthly, added to SOC therapy, in inducing favorable effects on LCBI & fibrous cap thickness in participants with AMI.
2. To demonstrate the superiority of ziltivekimab vs placebo once-monthly, added to SOC therapy, in inducing favorable effects on change in plaque burden as assessed by key metrics from Intra-Vascular Ultrasound (IVUS), Near Infrared Spectroscopy (NIRS), and Optical Coherence Tomography (OCT) in participants with AMI.
3. To compare the effects of ziltivekimab vs placebo once-monthly, both added to SOC therapy, on inflammatory and lipid biomarkers, as well as the relationship between levels of biomarkers and changes in plaque characteristics.
4. To compare the effects of ziltivekimab vs placebo once-monthly, both added to SOC therapy, on risk of cardiovascular events in participants with AMI.

Conditions and MedDRA coding

Acute myocardial infarction

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002840-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Acute myocardial infarction, with at least one coronary segment (culprit lesion) treated with PCI within 48 hours: a. Acute ST-segment elevation myocardial infarction (STEMI) with all of the following: i. Onset of relevant pain suggestive of cardiac ischemia within ≤24h of index angiography ii. ECG-changes (in the absence of left ventricular hypertrophy or left bundle branch block): ST-segment elevation at the J point in at least two contiguous leads ≥0.25 mV in men <40 years, ≥0.2 mV in men ≥40 years, or ≥0.15 mV in women in leads V2-V3; and/or ≥0.1 mV in all other leads. or b. Non-ST segment elevation myocardial infarction (NSTEMI), with rise and/or fall in cardiac troponin I or T with at least one value above the 99th percentile upper reference limit.
2. At least two major native coronary arteries (“study vessels”) each meeting the following criteria for intracoronary imaging immediately following the qualifying Percutaneous Coronary Intervention (PCI) procedure: a. Angiographic evidence of a reduction in lumen diameter between >20 and <50% by angiographic visual estimation b. Study vessel deemed to be accessible to imaging catheters and suitable for intracoronary imaging in the proximal (50 mm) segment (“study segment”) c. Study vessel may not be a bypass (saphenous vein or arterial) graft or a bypassed native vessel d. Study vessel must not have undergone previous PCI within the study segment e. A vessel which is candidate for intervention at the time of qualifying PCI or over the following 6 months in the judgment of the Investigator, cannot be a study vessel
3. Hemodynamic stability (as assessed by the treating physician) allowing the repetitive administration of nitroglycerine during the study specific imaging procedure

Exclusion criteria 10

1. Female of childbearing potential
2. Left-main disease, defined as ≥50% reduction in lumen diameter of the left main coronary artery by angiographic visual estimation
3. Three-vessel disease, defined as the presence of severe or significant CAD on the basis of angiography, imaging, or physiology, in all three major epicardial territories (including major branches) that have an indication for revascularization or are too advanced to be treated.
4. Significant coronary calcification or tortuosity deemed to preclude IVUS, NIRS and OCT evaluation.
5. Severe kidney impairment defined as any of the following a. Previous or current estimated glomerular filtration rate <30 ml/min/1.73m2 b. Chronic haemodialysis or peritoneal dialysis.
6. Active liver disease or hepatic dysfunction defined as at least one of the following: a. Previously known or current hepatic encephalopathy (clinical evaluation) b. Previously known or current ascites (clinical evaluation) c. Jaundice (clinical evaluation) d. Previous oesophageal/gastric variceal bleeding e. Known hepatitis cirrhosis
7. Known, or suspicion of, active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator
8. History of recurrent serious infections (infections leading to hospitalization or use of i.v. antibiotics) within the past 12 months, at the discretion of the investigator
9. Presence of risk factors for tuberculosis (TB) or history or evidence of latent TB such as (but not limited to): History or evidence of a positive TB test or chest X-ray compatible with prior TB and TB treatment initiated less than 28 days prior to randomisation
10. Major cardiac surgical (including but not restricted to coronary artery bypass graft surgery [CABG]), non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days or any major surgical procedure planned at the time of randomisation or as treatment for the current AMI (CABG).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in percent atheroma volume (PAV) as determined by greyscale IVUS in matched regions of interest. Measured from randomisation to end-of-study.

Secondary endpoints 12

1. Change in maximum lipid core burden index (LCBI) in any 4-mm segment (maxLCBI4mm) as determined by NIRS in matched regions of interest. Measured from randomisation to end-of-study.
2. Change in minimal fibrous cap thickness as determined by OCT in matched regions of interest. Measured from randomisation to end-of-study.
3. Change in LCBI total as determined by NIRS in matched regions of interest. Measured from randomisation to end-of-study.
4. Change in average angular extension (AAE) of macrophages as determined by OCT in matched regions of interest. Change in LCBI total as determined by NIRS in matched regions of interest. Measured from randomisation to end-of-study.
5. Change in normalized total atheroma volume (NTAV) by IVUS in matched regions of interest. Measured from randomisation to end-of-study.
6. Change in mean fibrous cap thickness as determined by OCT in matched regions of interest. Measured from randomisation to end-of-study.
7. Change in IL-6. Measured from randomisation to week 4 and week 52.
8. Change in hs-CRP. Measured from randomisation to to week 4 and week 52.
9. Change in hs-TnT . Measured from randomisation to week 4 and week 52.
10. Change in NT-pro-BNP . Measured from randomisation to week 4 and week 52.
11. Change in lipid and inflammatory markers. Measured from randomisation to week 4 and week 52.
12. Time to first occurrence of: All-cause death Cardiac death Non-fatal spontaneous myocardial infarction Any coronary revascularizationa Non-fatal stroke Transient ischemic attack Measured from randomisation to end-of-study.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 2

ECRI-trials B.V.

Sponsor organisation

ECRI-trials B.V.

Address

Westblaak 98

City

Rotterdam

Postcode

3012 KM

Country

Netherlands

Scientific contact point

Organisation

ECRI-trials B.V.

Contact name

EU Submission Hub

Public contact point

Organisation

ECRI-trials B.V.

Contact name

EU Submission Hub

Third parties 5

Sponsor responsibilities

Article 77 compliance

Novo Nordisk A/S

Contact point sponsor

Novo Nordisk A/S

Article 77 implementation

Novo Nordisk A/S

Locations

5 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 27 files

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

Application history

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