A Research Study to Look at the Effect of Ziltivekimab on Plaque in the Blood Vessels of the Heart, Compared to Placebo, in People With a Heart Attack

NCT07301034 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: NN6018-8195U1111-1316-8221
• Study Type: interventional
• Target: 332
• Locations: 6 countries
• Sites: 20

Brief Summary

The study is testing the effect of ziltivekimab on reducing plaque in the blood vessels of the heart, specifically aiming to manage or reduce atherosclerotic plaque. The purpose of the study is to determine whether ziltivekimab can effectively reduce this plaque. Participants will either receive ziltivekimab (the active medicine) or a placebo (a dummy medicine with no effect on the body), with the treatment assignment decided by chance. It is important to note that ziltivekimab is not yet approved in any country or region worldwide; therefore, it is a new medicine that doctors cannot prescribe. The study will last for about 15 months.

Conditions

Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• Change in percent atheroma volume (PAV) as determined by greyscale intravascular ultrasound (IVUS) in matched regions of interest

  Percentage (%).

  From randomisation (week 0) to end-of-study (52-week)

Secondary Outcomes (17)

• Change in maximum lipid core burden index (LCBI) in any 4-mm segment(maxLCBI4mm) as determined by Near-infrared spectroscopy (NIRS) in matched regions of interest

  From randomisation (week 0) to end-of-study (52-week)

• Change in minimal fibrous cap thickness as determined by (optical coherence tomography) OCT in matched regions of interest

  From randomisation (week 0) to end-of-study (52-week)

• Change in lipid core burden index (LCBI) total as determined by NIRS in matched regions of interest

  From randomisation (week 0) to end-of-study (52-week)

• Change in average angular extension (AAE) of macrophages as determined by OCT in matched regions of interest

  From randomisation (week 0) to end-of-study (52-week)

• Change in normalized total atheroma volume (NTAV) by IVUS in matched regions of interest

  From randomisation (week 0) to end-of-study (52-week)

Study Arms (2)

Ziltivekimab dose level 1 + standard of care (SOC)

EXPERIMENTAL

Participants receive dose level 1 of ziltivekimab along with standard of care (SOC) subcutaneously once monthly for 12 months.

Drug: Ziltivekimab

Placebo + SOC

PLACEBO COMPARATOR

Participants receive a placebo along with standard of care (SOC) subcutaneously once monthly for 12 months.

Drug: Ziltivekimab Placebo

Interventions

Ziltivekimab DRUG

Participants will receive ziltivekimab subcutaneously.

Ziltivekimab dose level 1 + standard of care (SOC)

Ziltivekimab Placebo DRUG

Participants will receive placebo matched to ziltivekimab subcutaneously.

Placebo + SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Age 18 years or above at the time of providing informed consent.
• Acute myocardial infarction, with at least one coronary segment (culprit lesion) treated with percutaneous coronary intervention (PCI):
• a. Acute ST-segment elevation myocardial infarction (STEMI) with all of the following: i. Onset of relevant pain suggestive of cardiac ischemia within less than or equal to (=\<) 24h of index angiography.
• ii. Electrocardiogram (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 greater than or equal to (\>=) 0.25 millivolts (mV) in men less than (\<) 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.
• 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.
• At least two major native coronary arteries ‡ ("study vessels") each meeting the following criteria for intracoronary imaging immediately following the qualifying PCI procedure:
• Angiographic evidence of a reduction in lumen diameter between \>20 and \<50 percent (%) by angiographic visual estimation.
• Study vessel deemed to be accessible to imaging catheters and suitable for intracoronary imaging in the proximal (50 millimeter \[mm\]) segment ("study segment").
• Study vessel may not be a bypass (saphenous vein or arterial) graft or a bypassed native vessel.
• Study vessel must not have undergone previous PCI within the study segment.
• 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.
• \. Hemodynamic stability (as assessed by the treating physician) allowing the repetitive administration of nitroglycerine during the study specific imaging procedure.
• \. Ability to understand the requirements of the study and to provide informed consent 7. Willingness to undergo follow-up intracoronary imaging. 8. Possibility for randomisation and administration of the loading dose as early as possible after invasive procedure and latest within 48 hours after index PCI.
• Two study segments may be obtained in the same vessel (e.g. two study segments in the Right Coronary Artery \[RCA\] or Left Circumflex Artery \[LCX\]), at the investigators discretion, considering vessel anatomy (e.g. left or right dominance), and where suitable landmarks between segments are at least 40 mm apart and with vessel wall irregularities.

You may not qualify if:

• Known or suspected hypersensitivity to study intervention(s) or related products.
• Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel.
• Previous participation in this study. Participation is defined as randomisation.
• Female of childbearing potential.
• Any condition, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• Left-main disease, defined as \>=50 percent (%) reduction in lumen diameter of the left main coronary artery by angiographic visual estimation
• Three-vessel disease, defined as the presence of severe or significant coronary artery disease (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.
• History of coronary artery bypass surgery
• Thrombolysis In Myocardial Infarction (TIMI) flow \<2 of the infarct-related artery after PCI
• Unstable clinical status (hemodynamic or electrical instability. Hemodynamic instability defined as any of the following:
• Killip Class III or IV. Sustained and/or symptomatic hypotension (as assessed by the treating physician).
• Significant coronary calcification or tortuosity deemed to preclude Intra-Vascular Ultrasound (IVUS), Near Infrared Spectroscopy (NIRS) and Optical Coherence Tomography (OCT) evaluation.
• Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening.
• Severe kidney impairment defined as any of the following:
• Previous or current estimated glomerular filtration rate \<30 milliliters per minute (ml/min) /1.73 square meter (m\^2) Chronic haemodialysis or peritoneal dialysis.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (20)

Medizinische Universität Wien

Vienna, 1090, Austria

NOT YET RECRUITING

Aalborg Universitetshospital Hjertemedicinsk Afdeling

Gistrup, 9260, Denmark

NOT YET RECRUITING

Rigshospitalet - Kardiologisk Forskningsenhed

København Ø, 2100, Denmark

NOT YET RECRUITING

Azienda Ospedaliera San Giovanni Addolorata

Rome, Lazio, 00184, Italy

NOT YET RECRUITING

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

NOT YET RECRUITING

DAI Scienze Mediche - UOC Endocrinologia

Messina, Sicily, 98124, Italy

NOT YET RECRUITING

Presidio Ospedaliero di Rivoli

Rivoli, To, 10098, Italy

NOT YET RECRUITING

Ospedale Policlinico San Martino

Genova, 16132, Italy

NOT YET RECRUITING

AOU Maggiore della Carità di Novara - Dipartimento Toraco-Cardio-Vascolare - SCDU Cardiologia

Novara, 28100, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche

Orbassano, 10043, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCS

Rome, 00168, Italy

NOT YET RECRUITING

IRCCS Policlinico San Donato

San Donato Milanese, 20097, Italy

NOT YET RECRUITING

Radboudumc

Nijmegen, 6525 GA, Netherlands

NOT YET RECRUITING

Erasmus MC

Rotterdam, 3015 GD, Netherlands

NOT YET RECRUITING

Hospital Universitario de la Princesa

Madrid, 28006, Spain

NOT YET RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

NOT YET RECRUITING

Universitäres Herzzentrum

Basel, 4031, Switzerland

RECRUITING

Inselspital-Universitätsklinik für Kardiologie

Bern, 3010, Switzerland

RECRUITING

HUG-Service de Cardiologie

Geneva, 1205, Switzerland

NOT YET RECRUITING

LUKS-Herzzentrum

Lucerne, 6000, Switzerland

RECRUITING

MeSH Terms

Conditions

Myocardial Infarction

Interventions

ziltivekimab

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Central Study Contacts

Novo Nordisk

CONTACT

(+1) 866-867-7178; clinicaltrials@novonordisk.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: December 24, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): November 14, 2028
• Study Completion (Estimated): February 24, 2029
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (2); ES (2); CH (4); AU (1); IT (9); NL (2)