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Myocardial InfarctionPhase 3ZEPHYRNCT07301034

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

A Phase 3 study testing Ziltivekimab in people with Myocardial Infarction, run by Novo Nordisk A/S at 20 sites in 6 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myocardial Infarction
What is being tested?
Ziltivekimab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
332 participants
Where
20 sitesin 6 countries
Study dates
18 Dec 2025to 24 Feb 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
  • 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.
  • 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.
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  • 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.
  • 5. Hemodynamic stability (as assessed by the treating physician) allowing the repetitive administration of nitroglycerine during the study specific imaging procedure.
  • 6. 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.

Who cannot join

  • 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.
  • Participation in any other interventional or imaging clinical study within the past 30 days, or as parallel inclusion during the index hospitalization.
  • Any condition, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
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  • 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.
  • Active liver disease or hepatic dysfunction defined as at least one of the following: Previously known or current hepatic encephalopathy (clinical evaluation) Previously known or current ascites (clinical evaluation) Jaundice (clinical evaluation) Previous oesophageal/gastric variceal bleeding Known hepatitis cirrhosis
  • Current use of anti-interleukin (IL)-6 products or anticipated use of such drugs any time during the study.
  • Use of systemic immunosuppressive drugs (both small molecules and biologics) or disease modifying anti-rheumatic drugs (DMARDs including both biologic DMARDs like anti- TNFalpha and conventional DMARDs like methotrexate) or anticipated chronic use of such drugs any time during the study. (Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary. Furthermore, temporary systemic immunosuppressive treatment of e.g., chronic obstructive pulmonary disease [COPD] exacerbations is allowed).
  • Known, or suspicion of, active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator.
  • History of recurrent serious infections (infections leading to hospitalization or use of intravenous (i.v.) antibiotics) within the past 12 months, at the discretion of the investigator.
  • Use of preventive systemic antibiotics, systemic antivirals, or systemic antifungals (Note: "Systemic" is defined as oral or i.v. drugs that are absorbed into the circulation. Antibiotics used to treat latent TB are exempted).
  • Absolute neutrophil count <2x10 10^9/L
  • Absolute platelet count < 120 x10^9/L
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >8 × upper limit of normal. Participants with increased levels of ALT or AST <=8 x upper limit of normal (ULN) are eligible at the discretion of the investigator if the investigator considers the ALT or AST elevations to be caused by the current AMI. In case the elevation is considered related to other reasons than the current AMI, participants should be excluded when ALT or AST >2.5 x(ULN).
  • Known (acute or chronic) hepatitis B or hepatitis C
  • Planned surgery within 12 months from the time of screening.
  • History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, low risk prostate cancer, or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN) at the discretion of the investigator.
  • Estimated life expectancy less than 2 years
  • 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 latent TB and TB treatment initiated less than 28 days prior to randomisation.
  • Diagnosis of human immunodeficiency virus (HIV).
  • History of gastrointestinal perforation (Note: History of perforated appendicitis more than 5 years old is not exclusionary).
  • History of active diverticulitis within the past 5 years.
  • History of inflammatory bowel disease that has been clinically active within the past 12 months.
  • History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the study.
  • Received a live or attenuated-live vaccine product within 4 weeks of study intervention administration or expected to receive a live or attenuated-live vaccine product during the treatment period.
  • 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).

Trial locations and contacts

20 sites in 6 countries. Contact the study team or a site near you to ask about taking part.

Novo Nordisk contact

(+1) 866-867-7178

clinicaltrials@novonordisk.com

20 sites in 6 countries

Italy9 sites, 9 recruiting

  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

    Bergamo, Lombardy, 24127

    Not yet recruiting

  • Ospedale Policlinico San Martino

    Genova, 16132

    Not yet recruiting

  • DAI Scienze Mediche - UOC Endocrinologia

    Messina, Sicily, 98124

    Not yet recruiting

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

    Novara, 28100

    Not yet recruiting

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

    Orbassano, 10043

    Not yet recruiting

  • Presidio Ospedaliero di Rivoli

    Rivoli, To, 10098

    Not yet recruiting

  • Azienda Ospedaliera San Giovanni Addolorata

    Rome, Lazio, 00184

    Not yet recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCS

    Rome, 00168

    Not yet recruiting

  • IRCCS Policlinico San Donato

    San Donato Milanese, 20097

    Not yet recruiting

Other trials in Italy

Switzerland4 sites, 4 recruiting

  • Universitäres Herzzentrum

    Basel, 4031

    Recruiting

  • Inselspital-Universitätsklinik für Kardiologie

    Bern, 3010

    Recruiting

  • HUG-Service de Cardiologie

    Geneva, 1205

    Not yet recruiting

  • LUKS-Herzzentrum

    Lucerne, 6000

    Recruiting

Other trials in Switzerland

Denmark2 sites, 2 recruiting

  • Aalborg Universitetshospital Hjertemedicinsk Afdeling

    Gistrup, 9260

    Not yet recruiting

  • Rigshospitalet - Kardiologisk Forskningsenhed

    København Ø, 2100

    Not yet recruiting

Other trials in Denmark

Netherlands2 sites, 2 recruiting

  • Radboudumc

    Nijmegen, 6525 GA

    Not yet recruiting

  • Erasmus MC

    Rotterdam, 3015 GD

    Not yet recruiting

Other trials in Netherlands

Spain2 sites, 2 recruiting

  • Hospital Universitario de la Princesa

    Madrid, 28006

    Not yet recruiting

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39008

    Not yet recruiting

Other trials in Spain

Austria1 site, 1 recruiting

  • Medizinische Universität Wien

    Vienna, 1090

    Not yet recruiting

Other trials in Austria

About this study

Official title: Effects of Ziltivekimab Versus Placebo on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction. A Serial, Multivessel, Intravascular Ultrasound, Near-infrared Spectroscopy and Optical Coherence Tomography Imaging Study

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.

Being tested
Ziltivekimab, Ziltivekimab Placebo
Medical subject headings
Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZiltivekimabDrug

    Participants will receive ziltivekimab subcutaneously.

  • Ziltivekimab PlaceboDrug

    Participants will receive placebo matched to ziltivekimab subcutaneously.

Study groups in NCT07301034
Study groupRoleWhat they receive
Ziltivekimab dose level 1 + standard of care (SOC)ExperimentalParticipants receive dose level 1 of ziltivekimab along with standard of care (SOC) subcutaneously once monthly for 12 months.
Receives: Drug: Ziltivekimab
Placebo + SOCPlacebo comparatorParticipants receive a placebo along with standard of care (SOC) subcutaneously once monthly for 12 months.
Receives: Drug: Ziltivekimab Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Percentage (%).

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

Secondary outcomes (17)

  1. 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

    Lipid core burden index (LCBI) (0 to 1000).

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

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

    Micro meter (µmeter).

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

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

    LCBI index (0 to 1000).

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

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

    Degrees (°).

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

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

    Cubic Millimeter (mm3).

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

  6. Change in mean fibrous cap thickness as determined by OCT in matched region of interest

    µmeter.

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

  7. Change in interleukin6 (IL-6)

    Picograms per milliliter (pg/mL).

    Measured: From randomisation (week 0) to week 4, and week 52

  8. Change in high-sensitivity C-reactive protein (hs-CRP)

    Milligrams per deciliter (mg/dL).

    Measured: From randomisation (week 0) to week 4, and week 52

  9. Change in high-sensitivity Troponin T (hs-TnT)

    Nanograms per milliliter (ng/mL).

    Measured: From randomisation (week 0) to week 4, and week 52

  10. Change in N-terminal-pro-brain natriuretic peptide (NT-pro-BNP)

    Picograms per milliliter (pg/mL).

    Measured: From randomisation (week 0) to week 4, and week 52

  11. Change in lipid and inflammatory markers

    Measured: From randomisation (week 0) to week 4, and week 52

  12. Time to first occurrence of: All-cause death

    Number of first occurrences and time-to-event.

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

  13. Time to first occurrence of: Cardiac death

    Number of first occurrences and time-to-event.

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

  14. Time to first occurrence of:Non-fatal spontaneous myocardial infarction

    Number of first occurrences and time-to-event.

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

  15. Time to first occurrence of: Any coronary revascularization

    Number of first occurrences and time-to-event.

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

  16. Time to first occurrence of: Non-fatal stroke

    Number of first occurrences and time-to-event.

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

  17. Time to first occurrence of:Transient ischemic attack

    Number of first occurrences and time-to-event.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2025
  2. Study start18 Dec 2025
  3. Primary completion14 Nov 2028 (estimated)
  4. Study completion24 Feb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
332 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07301034
Sponsor's protocol ID
NN6018-8195
Other IDs
U1111-1316-8221
Acronym
ZEPHYR
Status last verified
Mar 2026
First submitted
27 Nov 2025
Last updated
11 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ziltivekimab in people with Myocardial Infarction, run by Novo Nordisk A/S at 20 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy, Switzerland, Denmark, Netherlands, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Novo Nordisk ((+1) 866-867-7178, clinicaltrials@novonordisk.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in percent atheroma volume (PAV) as determined by greyscale intravascular ultrasound (IVUS) in matched regions of interest (time frame: From randomisation (week 0) to end-of-study (52-week)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07301034.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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