Table of contents

• Clinical trial overview
• Heart failure studies
• Cardiovascular disease and chronic kidney disease
• Coronary artery inflammation study
• Myocardial infarction studies
• Main endpoints and what they measure
• Who the trials are for

Clinical trial overview

Ziltivekimab is being studied in multiple interventional trials, which means the researchers give a treatment and compare it with a control such as placebo.^[1] The available studies are all authorised and are testing whether Ziltivekimab can improve outcomes in people with heart and blood vessel disease, often when inflammation is also present.^{[1][2][3][4][5][6]}

Most of the trials are Phase 3 studies, which are larger studies meant to test how well a treatment works in real patient groups.^{[1][2][4][5][6] One smaller study, SPIDER, is a Phase 4 trial, which usually means the treatment is being studied after it has already reached later-stage use in research.[3]}

Heart failure studies

Two trials focus on heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF), together with systemic inflammation.^{[1][5] HFmrEF means the heart pumps a slightly lower amount of blood than normal, while HFpEF means the pumping strength looks preserved but the heart does not fill or relax normally.[1][5]}

The HERMES study (NCT05636176) is a Phase 3 trial with 5,598 participants and compares Ziltivekimab with placebo, both added to standard care.^[1] Its main goal is to see whether treatment lowers the risk of cardiovascular death, heart failure hospitalisation, or an urgent heart failure visit.^[1]

The ATHENA study (2023-506988-34-00) is also Phase 3 and includes 680 participants.^[5] It looks at whether Ziltivekimab improves heart failure symptoms and physical function, using the KCCQ clinical summary score, which is a patient questionnaire about how heart failure affects daily life.^[5]

Cardiovascular disease and chronic kidney disease

The ZEUS study (2023-506926-35-00) is a Phase 3 trial in 6,200 people with atherosclerotic cardiovascular disease, chronic kidney disease, and systemic inflammation.^[2] Atherosclerotic cardiovascular disease means disease caused by buildup of fatty material in the arteries.^[2]

This study compares Ziltivekimab with placebo, both given with standard care, to see whether it lowers the risk of major adverse cardiovascular events.^[2] The main endpoint is time to first 3-point MACE, which includes cardiovascular death, non-fatal heart attack, and non-fatal stroke.^[2]

Coronary artery inflammation study

SPIDER (2024-515893-29-01) is a small Phase 4 study with 40 participants who have coronary artery disease.^[3] The trial is designed to study whether 20 weeks of Ziltivekimab can reduce inflammation in the artery wall and also lower systemic inflammatory tone.^[3]

Its main measures include changes in target to background ratio on imaging and changes in monocyte activation marker protein expression.^[3] In simple terms, this means the study is looking at imaging signs of inflammation and at blood cell markers linked to inflammation.^[3]

Myocardial infarction studies

Two trials focus on people who have had a heart attack, also called myocardial infarction.^{[4][6] One study, 2024-520364-34-00, includes 367 participants with acute myocardial infarction and tests whether Ziltivekimab can improve percent atheroma volume, which is a measure of plaque burden in the arteries.[4]}

The ARTEMIS study (NCT06118281) is a large Phase 3 trial with 8,540 adults who have type 1 acute myocardial infarction, including both STEMI and NSTEMI.^[6] STEMI and NSTEMI are two common types of heart attack, and the study starts treatment as early as possible after the event.^[6]

ARTEMIS aims to test whether Ziltivekimab reduces the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal heart attack, non-fatal stroke, and ischaemia-driven coronary revascularisation.^[6] Coronary revascularisation means a procedure to restore blood flow in the heart arteries.^[6]

Main endpoints and what they measure

A primary outcome or endpoint is the main result the researchers want to measure.^{[1][2][3][4][5][6] In these trials, the endpoints focus on serious clinical events, symptom scores, imaging results, and inflammation markers.[1][2][3][4][5][6]}

Examples include time to first cardiovascular death, heart failure hospitalisation, urgent heart failure visit, non-fatal heart attack, non-fatal stroke, and ischaemia-driven coronary revascularisation.^{[1][2][6] Other endpoints look at the KCCQ score, percent atheroma volume, target to background ratio, and monocyte activation markers.[3][4][5]}

Who the trials are for

The studies recruit different patient groups, but they all involve people with a high risk of heart and blood vessel problems.^{[1][2][3][4][5][6] Some trials focus on people with heart failure and systemic inflammation, while others include people with chronic kidney disease, coronary artery disease, or a recent heart attack.[1][2][3][4][5][6]}

Across the studies, the researchers are trying to learn whether Ziltivekimab can reduce serious events and improve important measures of disease activity in these patient groups.^{[1][2][3][4][5][6]}