Ziltivekimab: Zilitivekimab will be administered subcutaneously once-monthly.
Placebo: Placebo matched to ziltivekimab will be administered subcutaneously once-monthly.
Study summary
The study is being done to see if ziltivekimab can be used to treat participants living with heart failure and inflammation. Participants will either get ziltivekimab (active medicine) or placebo (inactive substance that looks like the study medicine but does not contain any medicine). The treatment participants get is decided by chance. Participant's chance of getting ziltivekimab or placebo is the same. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe. The study is expected to last for up to 1 year and 4 months.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligrams per liter (mg/L) at screening (visit 1)
* Disease specific - cardiovascular:
* N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than or equal to 225 picograms per milliliter (pg/mL) (375 pg/mL for participants with atrial fibrillation/flutter) at screening
* Diagnosis of heart failure (New York heart association (NYHA) Class II-III)
* Left ventricular ejection fraction (LVEF) greater than 40 percent documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (example myocardial infarction (MI) or heart failure (HF) hospitalisation)
* Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following:
1. Left atrial (LA) volume index greater than 34 milliliter per square meter (mL/m\^2)
2. LA diameter greater than or equal to 3.8 centimeters (cm)
3. LA length greater than or equal to 5.0 cm
4. LA area greater than or equal to 20 square centimeters (cm\^2)
5. LA volume greater than or equal to 55 milliliters (mL)
6. Intraventricular septal thickness greater than or equal to 1.1 cm
7. Posterior wall thickness greater than or equal to 1.1 cm
8. LV mass index greater than or equal to 115 grams per square meter (g/m\^2) in men or greater than or equal to 95 g/m\^2 in women
h) E/e' (mean septal and lateral) greater than or equal to 10 i) e' (mean septal and lateral) less than 9 centimeters per second (cm/s)
* No heart failure hospitalisations or urgent heart failure visits between screening and randomisation
* Able to perform the 6-minute walk test (6MWT) at screening with a minimum distance of 100 metres
* Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score lesser than 80 at screening
Exclusion Criteria:
* Medical conditions - cardiovascular:
* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation within 30 days prior to screening (visit 1)
* Systolic blood pressure greater than or equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than or equal to 3 antihypertensive drugs
* Heart rate above 110 or below 40 beats per minute as evaluated on the Electrocardiogram (ECG) performed at screening (visit 1)
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1)
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1)
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2)
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including chronic obstructive pulmonary disease (COPD)
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism)
* Medical conditions - infections/immunosuppression:
* Clinical evidence of, or suspicion of, active infection at the discretion of the investigator
Primary outcome measure(s)
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (KCCQ-CSS) — From randomisation (month 0) to end-of-treatment (month 12) Measured as score (score on scale; range; 0-100). The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
Trial sites (217)
Facility
City
Region
Status
Advanced Cardiovascular, LLC
Alexander City
Alabama
Eastern Shore Rsrch Inst, LLC
Fairhope
Alabama
Cardiology & Medicine Clinic
Little Rock
Arkansas
Valley Clinical Trials, Inc.
Northridge
California
UCI Health
Orange
California
South California Heart Spc
Pasadena
California
Clearwater Cardiovascular Consultants
Largo
Florida
Ocala Cardiovascular Research
Ocala
Florida
Ormond Beach Clinical Research
Ormond Beach
Florida
St Johns Ctr Clin Rsch-St. Aug
Saint Augustine
Florida
GA Arrhythmia Cons & Rsch Inst
Macon
Georgia
Velocity Clin Rsrch - Savannah
Savannah
Georgia
Chicago Medical Research LLC
Hazel Crest
Illinois
UofL Health Care Outpatient
Louisville
Kentucky
Maryland Cardiovascular Specialists - Baltimore
Baltimore
Maryland
MD Medical Research
Oxon Hill
Maryland
Cardio and Vascular Assoc-CAVA
Bloomfield Hills
Michigan
Millennium Cardiology
Farmington Hills
Michigan
Kansas City VA Medical Center
Kansas City
Missouri
Washington University
St Louis
Missouri
Renown Regional Medical Center
Reno
Nevada
Long Island Cardiovascular Consultants PC
Lake Success
New York
Mount Sinai Hosp at NYC
New York
New York
Northwell Health Phys Cardio
Riverhead
New York
University Of North Carolina At Chapel Hill
Chapel Hill
North Carolina
AMS Cardiology
Horsham
Pennsylvania
Univ of Pennsylvania Hospital
Philadelphia
Pennsylvania
PharmaTex Research
Amarillo
Texas
University of Texas Southwestern Medical Center
Dallas
Texas
David Turbay, MD, PLLC
El Paso
Texas
Private Practice Leadership LLC.
Katy
Texas
Clinical Advancement Center
San Antonio
Texas
Clinical Advancement Ctr, PLLC
San Antonio
Texas
Sherman Clinical Research
Sherman
Texas
Northwest Heart Center
Tomball
Texas
Sentara Health Research Center
Norfolk
Virginia
Virginia Commonwealth University
Richmond
Virginia
Cardiología Palermo
City of Buenos Aires
Buenos Aires
Centro Médico CIMEL
Lanús Este
Buenos Aires
Instituto de Investigaciones Clinicas Quilmes SRL
Buenos Aires
Argentina
+ 177 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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