Effects of Ziltivekimab on Coronary Atherosclerotic Burden in Patients With Acute Myocardial Infarction (ZEPHYR)

March 20, 2026 updated by: ECRI bv

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

Despite improvements in the treatment, coronary artery disease (CAD) remains one of the leading causes of death worldwide. Around 20% of people who have suffered a heart attack (myocardial infarction) need to be hospitalized again within a year, and 10% experience another heart attack. Despite currently available medication, patients remain at risk of further episodes after a heart attack. Scientists have discovered that inflammation in the body plays a decisive role in the development and narrowing of arterial blockages (atherosclerosis). This study aims to investigate whether a new treatment that reduces inflammation can help improve the arteries of patients with CAD.

This study will examine whether blocking certain inflammation-related substances with a new medicinal product called ziltivekimab affects the buildup and composition of plaques (fatty deposits) in the coronary arteries. Special imaging diagnostic techniques will be used to look inside the arteries and check whether the treatment helps reduce the narrowing caused by dangerous plaques, which can lead to future heart attacks.

This is a clinical study in which participants are randomly divided into two groups (randomization): one group will receive the new treatment ziltivekimab and other group will receive a placebo (a harmless substance with no active ingredients). Both groups will continue to receive standard treatment for heart attacks. The study lasts approximately 15 months per participant.

The full scientific title of the trial is: Effects of ziltivekimab versus placebo on coronary atherosclerosis in patients with acute myocardial infarction. A study with serial multi-vessel imaging obtained using intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography techniques.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite advances in cardiovascular care and preventive treatments, coronary artery disease (CAD) still represents the leading causes of death worldwide. Almost one fifth of patients with acute myocardial infarction (MI) suffer from rehospitalization within 1 year and 10% from recurrent MI. This residual cardiovascular risk persists regardless of optimal medical therapy with contemporary pharmacologic treatments including lipid lowering drugs, suggesting that this excess risk is mediated through pathways not yet directly addressed by current management. Inflammation is now a well-acknowledged major contributor to atherosclerosis development and plaque progression/instability, with both the innate (monocyte-derived macrophages) and the acquired immune system (T-cells) thought to be involved. Within atherosclerotic human plaques, activated monocyte-derived macrophages, specialized CD4+ and CD8+ T-cells produce a wide array of chemokines and cytokines with pro-inflammatory effects.

Despite a growing body of evidence that has confirmed anti-inflammatory therapy as a new cornerstone opportunity to reduce effectively the residual cardiovascular risk in CAD patients with CAD treated with optimal medical therapy, the direct effect of these therapies on atherosclerosis extension and composition is largely unknown. Convincing experimental evidence has raised the translational hypothesis of a direct favourable effect of IL-6 inhibition on plaque biology and stabilization. However, in-human data regarding the mechanistic role of anti-IL-6 agents on coronary atherosclerosis are lacking so far.

The purpose of this study is to investigate for the first time the in-vivo effects of IL-1/IL-6 pathway inhibition on coronary plaque morphology and composition in patients with CAD. Serial multi-vessel images obtained with multimodality intracoronary imaging will allow for a comprehensive evaluation of presumed high risk atherosclerotic features such as plaque burden, fibrous cap thickness, lipid content and local inflammation. An intracoronary serial imaging study may elucidate the exact pathophysiological underpinnings of atheroprotection beyond lipid lowering therapy and assess whether an effective anti-inflammatory therapy can improve the atherosclerotic profile of patients with CAD.

This is an interventional, randomised, parallel-group, double-blind, placebo-controlled, multi-centre, multi-national study designed to evaluate the effects of ziltivekimab versus placebo (randomised 1:1), both administered s.c. once-monthly and added to standard of care, on change in percent atheroma volume (PAV) as well as change in maxLCBI and fibrous cap thickness. The initial dose of ziltivekimab s.c./placebo to be administered at randomisation which is as early as possible and latest within 48 hours after the index PCI procedure, followed by once-monthly administration during the treatment period.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
332

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Switzerland
      • Bern, Switzerland
        • Recruiting
        • Bern University Hospital, Inselspital Bern
        • Contact:
          • Lorenz Räber, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Informed consent obtained before any study-related activities.
  • 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 PCI.
  • At least two major native coronary arteries each meeting angiographic criteria for intracoronary imaging immediately following the qualifying PCI procedure.

Key Exclusion Criteria:

  • Known or suspected hypersensitivity to study intervention(s) or related products.
  • Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel.
  • Female of childbearing potential.
  • Left-main disease.
  • Three-vessel disease.
  • History of coronary artery bypass surgery.
  • TIMI flow <2 of the infarct-related artery after PCI.
  • Unstable clinical status (hemodynamic or electrical instability.
  • Significant coronary calcification or tortuosity deemed to preclude IVUS, NIRS and OCT evaluation.
  • Uncontrolled cardiac arrhythmia.
  • Severe kidney impairment.
  • Active liver disease or hepatic dysfunction.
  • Current use of anti-IL-6 products or anticipated use of such drugs any time during the study.
  • Use of systemic immunosuppressive drugs or disease modifying anti-rheumatic drugs or anticipated chronic use of such drugs any time during the study.
  • Known, or suspicion of, active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator
  • History of recurrent serious infections.
  • Use of preventive systemic antibiotics, systemic antivirals, or systemic antifungals.
  • 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
  • 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 within the past 60 days or any major surgical procedure planned at the time of randomisation or as treatment for the current AMI (CABG).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ziltivekimab Arm
Participants will receive Ziltivekimab subcutaneously once per month
Drug: Ziltivekimab
Ziltivekimab is administered subcutaneously (i.e., under the skin) once per month added to standard of care.
Placebo Comparator: Placebo Arm
Participants will receive placebo subcutaneously once per month
Drug: Placebo
Placebo is administered subcutaneously (i.e., under the skin) once per month added to standard of care.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in percent atheroma volume
Time Frame: From randomization (week 0) to end-of-study (52-week)
Change in percent atheroma volume (PAV) as determined by greyscale intravascular ultrasound (IVUS) in matched regions of interest. Theoretical change is between -100% to +100%. Typical range around -2% to +2%. A lower (more negative) change in PAV is better.
From randomization (week 0) to end-of-study (52-week)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum lipid core burden index
Time Frame: From randomisation (week 0) to end-of-study (52-week)
Change in maximum lipid core burden index (LCBI) in any 4-mm segment (maxLCBI4mm) as determined by NIRS in matched regions of interest. Theoretical range is between -1000 to +1000. Typical range around -250 to +250. A lower (more negative) change is better.
From randomisation (week 0) to end-of-study (52-week)
Minimal fibrous cap thickness
Time Frame: 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. Theoretical range is between -500 µm to +500 µm. Typical range around -50 µm to +110 µm. A higher (positive) change is better; it indicates fibrous cap thickening (increased plaque stability).
From randomisation (week 0) to end-of-study (52-week)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ECRI bv

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novo Nordisk A/S
Cardialysis B.V.
Insel Gruppe AG, University Hospital Bern

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Ernest Spitzer, MD, European Cardiovascular Research Institute
  • Principal Investigator: Lorenz Räber, MD, PhD, Cardiology Department, Bern University Hospital, Inselspital Bern, Switzerland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 19, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 28, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ECRI-16
  • 2024-520364-34-00 (Ctis)
  • NN6018-8195 (Other Identifier: Novo Nordisk A/S)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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