Coronary Artery DiseasePhase 3ZEPHYRNCT07276282
Effects of Ziltivekimab on Coronary Atherosclerotic Burden in Patients With Acute Myocardial Infarction
A Phase 3 study testing Ziltivekimab in people with Coronary Artery Disease and Acute Myocardial Infarction (AMI), run by ECRI bv at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Acute Myocardial Infarction (AMI), Coronary Atherosclerosis of Native Coronary Artery
- 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
- 1 siteSwitzerland
- Study dates
- 19 Dec 2025to 1 Dec 2028
- 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.
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Bern University Hospital, Inselspital Bern
Bern
Lorenz Räber, MD, PhD
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
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.
Read more
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.
Read the 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.
- Conditions
- Coronary Artery Disease, Acute Myocardial Infarction (AMI), Coronary Atherosclerosis of Native Coronary Artery
- Being tested
- Ziltivekimab, Placebo
- Keywords
- IL-6 inhibition, atherosclerosis, acute myocardial infarction, anti-inflammatory, intracoronary imaging
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiltivekimabDrug
Ziltivekimab is administered subcutaneously (i.e., under the skin) once per month added to standard of care.
PlaceboDrug
Placebo is administered subcutaneously (i.e., under the skin) once per month added to standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Ziltivekimab Arm | Experimental | Participants will receive Ziltivekimab subcutaneously once per month Receives: Drug: Ziltivekimab |
| Placebo Arm | Placebo comparator | Participants will receive placebo subcutaneously once per month Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in percent atheroma volume
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.
Measured: From randomization (week 0) to end-of-study (52-week)
Secondary outcomes (2)
Maximum lipid core burden index
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.
Measured: From randomisation (week 0) to end-of-study (52-week)
Minimal fibrous cap thickness
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).
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.
- First posted11 Dec 2025
- Study start19 Dec 2025
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- ECRI bv
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novo Nordisk A/S, Insel Gruppe AG, University Hospital Bern, Cardialysis B.V.
- Responsible party
- Sponsor
- Investigators
- Lorenz Räber, MD, PhD, Principal investigator, Cardiology Department, Bern University Hospital, Inselspital Bern, SwitzerlandErnest Spitzer, MD, Study director, European Cardiovascular Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07276282
- Sponsor's protocol ID
- ECRI-16
- Other IDs
- 2024-520364-34-00, NN6018-8195
- Acronym
- ZEPHYR
- Status last verified
- Mar 2026
- First submitted
- 28 Nov 2025
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07276282
- Acronym / sponsor ID
- ZEPHYR / ECRI-16
- Conditions
- Coronary Artery Disease, Acute Myocardial Infarction (AMI), Coronary Atherosclerosis of Native Coronary Artery
- Keywords
- IL-6 inhibition, atherosclerosis, acute myocardial infarction, anti-inflammatory, intracoronary imaging
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 332 participants (estimated)
- Lead sponsor
- ECRI bvIndustry (pharma, biotech, devices)
- Collaborators
- Novo Nordisk A/S, Insel Gruppe AG, University Hospital Bern, Cardialysis B.V.
- Study start
- 19 Dec 2025 (actual)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 11 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ziltivekimab Arm | Experimental | Drug: ZiltivekimabParticipants will receive Ziltivekimab subcutaneously once per month |
| Placebo Arm | Placebo comparator | Drug: PlaceboParticipants will receive placebo subcutaneously once per month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZiltivekimabZiltivekimab is administered subcutaneously (i.e., under the skin) once per month added to standard of care. | Drug | Ziltivekimab Arm |
| PlaceboPlacebo is administered subcutaneously (i.e., under the skin) once per month added to standard of care. | Drug | Placebo Arm |
Primary outcome
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.
2 secondary outcomes
Maximum lipid core burden index
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lorenz Räber, MD, PhD principal investigator
Cardiology Department, Bern University Hospital, Inselspital Bern, Switzerland
Ernest Spitzer, MD study director
European Cardiovascular Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ziltivekimab in people with Coronary Artery Disease and Acute Myocardial Infarction (AMI), run by ECRI bv at 1 site in Switzerland.
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 4 inclusion and 23 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 23 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 1 site in Switzerland. 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 Anita Dekker (31102062828, adekker@cardialysis.nl), 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 (time frame: From randomization (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?
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 23 Mar 2026.