A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation (ATHENA)

Effects of Ziltivekimab Versus Placebo on Heart Failure Symptoms and Physical Function in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Systemic Inflammation

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Systemic Inflammation
• Intervention / Treatment: Drug: Ziltivekimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 680
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AGC
    • Not yet recruiting
    • Centro Medico Dra. Laura Maffei e Investigacion Clínica Apli
  • Buenos Aires, Argentina, B1878GEG
    • Not yet recruiting
    • Instituto de Investigaciones Clinicas Quilmes SRL
  • Caba, Argentina, C1061AAS
    • Not yet recruiting
    • Centro de Investigación y Prevención Cardiovascular
  • Lanus Este, Argentina, B1824KAJ
    • Not yet recruiting
    • Centro Médico CIMEL
  • Morón, Argentina, B1708IFF
    • Not yet recruiting
    • Consultorio Integral de Atención al Diabético
  • Salta, Argentina, 4400
    • Not yet recruiting
    • Centro Cardiovascular Salta
  • San Miguel De Tucumán, Tucumán., Argentina, T4000
    • Not yet recruiting
    • Investigaciones Clínicas Tucumán
• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Not yet recruiting
      • John Hunter Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • Not yet recruiting
      • The Prince Charles Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Not yet recruiting
      • Ballarat Base Hospital
    • Epping, Victoria, Australia, 3076
      • Not yet recruiting
      • The Cardiologists Pty Ltd
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Not yet recruiting
      • Fiona Stanley Hospital Cardiology
• Bulgaria
  • Haskovo, Bulgaria, 6300
    • Recruiting
    • MHAT Haskovo AD
  • Pleven, Bulgaria, 5800
    • Recruiting
    • UMHAT Heart and Brain
  • Plovdiv, Bulgaria, 4002
    • Not yet recruiting
    • "UMHAT "Sveti Georgi" EAD
  • Sofia, Bulgaria, 1750
    • Recruiting
    • "UMHAT "Sveta Anna" Sofia" AD, Clinic of Cardiology
  • Sofia, Bulgaria, 1510
    • Not yet recruiting
    • "Medical Center Hera" EOOD - Sofia
  • Sofia, Bulgaria, 1527
    • Not yet recruiting
    • Medico-dental center ISUL - Tsaritsa Yoanna EOOD
  • Sofia, Bulgaria, 1606
    • Not yet recruiting
    • "UMHATEM N.I. Pirogov" EAD
• Canada
  • Quebec, Canada, G1R 2J6
    • Not yet recruiting
    • CHU de Quebec-Uni Laval-Hotel
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Not yet recruiting
      • University of Calgary_Calgary
  • Ontario
    • Cambridge, Ontario, Canada, N1R 6V6
      • Not yet recruiting
      • Cambridge Cardiac Care Centre
    • Cambridge, Ontario, Canada, N1R 7R1
      • Not yet recruiting
      • Saul Vizel Pro. Med. Corp
    • Scarborough, Ontario, Canada, M1B 5N1
      • Withdrawn
      • Corcare Cardiovascular Research
    • Toronto, Ontario, Canada, M6G 1M2
      • Recruiting
      • Diabetes Heart Research Centre
    • Waterloo, Ontario, Canada, N2T 0C1
      • Recruiting
      • CPS Research
    • Waterloo, Ontario, Canada, N2T OC1
      • Not yet recruiting
      • Clinical Research Solutions Inc.
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Not yet recruiting
      • Institut de Cardiologie de Montreal
    • Montreal, Quebec, Canada, H3G 1A4
      • Not yet recruiting
      • Montreal General Hospital
• Czechia
  • Brno, Czechia, 612 00
    • Not yet recruiting
    • Kardiologicka ambulance Brno s.r.o.
  • Brno, Czechia, 63600
    • Recruiting
    • Vojenska nemocnice Brno
  • Praha 7, Czechia, 170 00
    • Not yet recruiting
    • Poliklinika Holešovice VISIONARY - MEDICON a.s.
  • Svitavy, Czechia, 568 25
    • Not yet recruiting
    • Svitavska nemocnice Kardiologie
  • Trutnov, Czechia, 541 01
    • Not yet recruiting
    • Kardiologie Trutnov Ferkl
• France
  • Poitiers, France, 86000
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Poitiers
  • Rennes, France, 35000
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou
  • Rouen cedex, France, 76031
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
  • Toulon, France, 83100
    • Not yet recruiting
    • Centre Hospitalier Intercommunal Toulon La Seine-Sur-Mer - Hopital Sainte Musse
  • Vandoeuvre Les Nancy, France, 54500
    • Not yet recruiting
    • Chru de Nancy - Hopital Brabois
• Germany
  • Dresden, Germany, 01307
    • Not yet recruiting
    • Herzzentrum Dresden GmbH Universitätsklinik
  • Elsterwerda, Germany, 04910
    • Not yet recruiting
    • Zentrum fuer klinische Studien Suedbrandenburg GmbH
  • Frankfurt, Germany, 60389
    • Recruiting
    • MVZ CCB Frankfurt Und Main-Taunus GbR
  • Freiburg, Germany, 79106
    • Not yet recruiting
    • Medical Center - University Of Freiburg
  • Homburg, Germany, 66424
    • Not yet recruiting
    • UKS - Innere Medizin III
  • Kaiserslautern, Germany, 67655
    • Not yet recruiting
    • Kardiopraxis Schirmer
• Greece
  • Athens, Greece, 10676
    • Not yet recruiting
    • Evangelismos Hospital
  • Athens, Greece, GR-15123
    • Recruiting
    • "Hygeia" General Hospital of Athens
  • Athens, Greece, 11527
    • Not yet recruiting
    • 'G. Gennimatas' General Hospital of Athens
  • Athens, Greece, GR-14233
    • Not yet recruiting
    • Konstantopouleio G.H. of Athens, "Agia Olga"
  • Chaidari, Athens, Greece, GR-12462
    • Not yet recruiting
    • U.G.H of Athens "Attikon"
  • Chios, Greece, GR82100
    • Not yet recruiting
    • General Hospital of Chios "Skilitsio"
  • Larissa, Greece, GR-41110
    • Not yet recruiting
    • Univ Gen Hospital Larisa, Cardiology Medicine Clinic
  • Thessaloniki, Greece, 54636
    • Not yet recruiting
    • "AHEPA" University General Hospital of Thessaloniki
  • Thessaloniki, Greece, GR-57010
    • Not yet recruiting
    • Gen Hospital of Thessaloniki G.Papanikolaou,Cardiology Dpt
  • Thessaloniki, Greece, GR54642
    • Not yet recruiting
    • 'Ippokrateio' General Hospital of Thessaloniki
  • Attiki
    • Athens, Attiki, Greece, GR11528
      • Not yet recruiting
      • Alexandra General Hospital, Therapeutic Clinic
• India
  • Puducherry, India, 605006
    • Not yet recruiting
    • Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)
  • Andhra Pradesh
    • Vijaywada, Andhra Pradesh, India, 520008
      • Recruiting
      • Siddhartha Medical College & Government General Hospital
  • Andra Pradesh
    • Visakhapatnam, Andra Pradesh, India, 530002
      • Not yet recruiting
      • King George Hospital
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Not yet recruiting
      • Sir Ganga Ram Hospital
    • New Delhi, Delhi, India, 110029
      • Not yet recruiting
      • All India Institute Of Medical Sciences (AIIMS)
    • New Delhi, Delhi, India, 110002
      • Not yet recruiting
      • G B Pant Institute of Postgraduate Medical Education and Research
    • New Delhi, Delhi, India, 110029
      • Not yet recruiting
      • Vardhaman Mahavir Medical College & Safdarjung Hospital
    • New Delhi, Delhi, India, 110093
      • Not yet recruiting
      • Rajiv Gandhi Super Speciality Hospital
  • Gujarat
    • Vadodara, Gujarat, India, 390022
      • Recruiting
      • Rhythm Heart Institute
  • Karnataka
    • Belagavi, Karnataka, India, 590010
      • Not yet recruiting
      • KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
    • Bengaluru, Karnataka, India, 560069
      • Not yet recruiting
      • Sri Jayadeva Institute of Cardiovascular Sciences & Research
    • Bengaluru, Karnataka, India, 560034
      • Not yet recruiting
      • St John's Medical College Hospital
    • Mysuru, Karnataka, India, 570015
      • Recruiting
      • Manipal Hospital, Mysuru
    • Udupi, Karnataka, India, 576104
      • Not yet recruiting
      • Kasturba Medical College and Hospital, Manipal
  • Maharashtra
    • Nagpur, Maharashtra, India, 441108
      • Not yet recruiting
      • All India Institute of Medical Sciences (AIIMS), Nagpur
    • Nagpur, Maharashtra, India, 440033
      • Recruiting
      • Sengupta Hospital and Research Institute
    • Nashik, Maharashtra, India, 422005
      • Not yet recruiting
      • Vijan Hospital & Research Centre
    • Nashik, Maharashtra, India, 422005
      • Recruiting
      • Vijan Hospital & Research Centre
    • Nashik, Maharashtra, India, 422005
      • Not yet recruiting
      • Chopda Medicare and Research Centre Pvt. Ltd.
    • Pune, Maharashtra, India, 411028
      • Recruiting
      • Villoo Poonawalla Memorial Hospital
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • Not yet recruiting
      • All India Institute of Medical Sciences (AIIMS), Bhubaneswar
  • Rajasthan
    • Bikaner, Rajasthan, India, 334003
      • Not yet recruiting
      • S.P. Medical College & Associated Group of Hospitals
  • Telangana
    • Hyderabad, Telangana, India, 500020
      • Not yet recruiting
      • Guru Nanak CARE Hospitals
    • Hyderabad, Telangana, India, 500055
      • Not yet recruiting
      • Malla Reddy Narayana Multispeciality Hospital
  • Uttar Pradesh
    • Aligarh, Uttar Pradesh, India, 202001
      • Not yet recruiting
      • Jawaharlal Nehru Medical College and Hospital
    • Kanpur, Uttar Pradesh, India, 208002
      • Not yet recruiting
      • Ganesh Shankar Vidyarthe Memorial Medical College (GSVM Medical College)
    • Lucknow, Uttar Pradesh, India, 226014
      • Not yet recruiting
      • Sanjay Gandhi Postgraduate Institute of Medical Sciences
    • Lucknow, Uttar Pradesh, India, 226010
      • Not yet recruiting
      • Dr. Ram Manohar Lohia Institute of Medical Sciences
  • West Bengal
    • Kolkata, West Bengal, India, 700027
      • Not yet recruiting
      • B M Birla Heart Research Centre
• Malaysia
  • Kajang, Malaysia, 43000
    • Not yet recruiting
    • Hospital Serdang
  • Kota Bharu, Kelantan, Malaysia, 15586
    • Not yet recruiting
    • Hospital Raja Perempuan Zainab II
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Not yet recruiting
      • Hospital Sultanah Aminah
  • Kedah
    • Alor Setar, Kedah, Malaysia, 05460
      • Not yet recruiting
      • Hospital Sultanah Bahiyah
  • Pahang
    • Kuantan, Pahang, Malaysia, 25100
      • Not yet recruiting
      • Hospital Tengku Ampuan Afzan
  • Perak
    • Ipoh, Perak, Malaysia, 30540
      • Not yet recruiting
      • Hospital Raja Permaisuri Bainun Ipoh
  • Wilayah Persekutuan Kuala Lumpur
    • Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia, 59100
      • Not yet recruiting
      • University Malaya Medical Centre
• Poland
  • Bydgoszcz, Poland, 85-681
    • Not yet recruiting
    • 10 Wojskowy Szpital Kliniczny z Polikliniką - Samodzielny Publiczny Zakład Opieki Zdrowotnej w Bydgoszczy
  • Gdynia, Poland, 81-157
    • Recruiting
    • Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman
  • Gdynia, Poland, 81-348
    • Not yet recruiting
    • Szpitale Pomorskie Sp. z o.o.
  • Poznan, Poland, 61-848
    • Not yet recruiting
    • Uniwersytecki Szpital Kliniczny W Poznaniu
  • Warszawa, Poland, 02-507
    • Not yet recruiting
    • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
  • Dolnoslaskie
    • Jelenia Góra, Dolnoslaskie, Poland, 58-506
      • Not yet recruiting
      • Pratia S.A.
  • Kujawsko-Pomorskie
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-605
      • Recruiting
      • Centrum Medyczne Intercor Sp. z o.o.
  • Lodzkie
    • Lodz, Lodzkie, Poland, 90-549
      • Recruiting
      • Uniwersytecki Szpital Kliniczny Im Wojskowej Akademii Medycznej Centralny Szpital Weteranow
  • Lubelskie
    • Pulawy, Lubelskie, Poland, 24-100
      • Not yet recruiting
      • Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Pulawach
  • Malopolskie
    • Kraków, Malopolskie, Poland, 30-002
      • Not yet recruiting
      • Cardiomedicum Sp. z o.o.
    • Oswiecim, Malopolskie, Poland, 32-600
      • Not yet recruiting
      • Formed 2 Sp. z o.o.
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-540
      • Not yet recruiting
      • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-348
      • Not yet recruiting
      • Szpitale Pomorskie Sp. z o.o.
• Portugal
  • Guilhufe - Penafiel, Portugal, 4560-136
    • Not yet recruiting
    • CHTâmega e Sousa - Hospital Padre Américo
  • Lisboa, Portugal, 1500-650
    • Not yet recruiting
    • Hospital da Luz
  • Lisboa, Portugal, 1649-035
    • Not yet recruiting
    • Centro Hospitalar Lisboa Norte
  • Lisbon, Portugal, 1449-005
    • Not yet recruiting
    • CHLO, EPE - Hospital São Francisco Xavier
  • Setubal, Portugal, 2910-446
    • Not yet recruiting
    • Centro Hospitalar de Setubal
• Spain
  • Madrid, Spain, 28034
    • Not yet recruiting
    • Hospital Ramon y Cajal
  • Sanlúcar de Barrameda, Spain, 11540
    • Not yet recruiting
    • Hospital Virgen del Camino - Sanlúcar de Barrameda
  • Santiago de Compostela, Spain, 15706
    • Not yet recruiting
    • Complejo Hospitalario Universitario de Santiago
  • Sevilla, Spain, 41003
    • Not yet recruiting
    • Clínica Nuevas Tecnologías en Diabetes y Endocrinología
  • Sevilla, Spain, 41950
    • Not yet recruiting
    • Hospital Nisa Sevilla Aljarafe
  • Valencia, Spain, 46010
    • Not yet recruiting
    • Fundación para la Investigación del Hospital Clínico de Valencia (INCLIVA)
  • Castilla Y León
    • Salamanca, Castilla Y León, Spain, 37007
      • Not yet recruiting
      • Hospital Universitario de Salamanca
• Turkey
  • Adana, Turkey, 01000
    • Not yet recruiting
    • T.C. Saglık Bakanlıgı Adana Sehir Egitim ve Arastirma Hastan
  • Afyon, Turkey, 03200
    • Not yet recruiting
    • Afyonkarahisar Health Sciences University
  • Ankara, Turkey, 06800
    • Not yet recruiting
    • Ankara Sehir Hastanesi Cardiology
  • Bursa, Turkey, 16110
    • Not yet recruiting
    • Bursa Sehir Hastanesi Cardiology
  • Edirne, Turkey, 22030
    • Not yet recruiting
    • Trakya University
  • Istanbul, Turkey, 34480
    • Not yet recruiting
    • Basaksehir Cam ve Sakura Sehir Hastanesi
  • Kayseri, Turkey, 38039
    • Not yet recruiting
    • Erciyes University Cardiology
  • Kocaeli, Turkey, 41380
    • Not yet recruiting
    • Kocaeli Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Not yet recruiting
    • Ninewells Hospital
  • Peterborough, United Kingdom, PE3 9GZ
    • Not yet recruiting
    • Peterborough City Hospital
  • West Sussex, United Kingdom, PO19 6SE
    • Recruiting
    • St. Richards Hospital
  • Highland
    • Inverness, Highland, United Kingdom, IV2 3JH
      • Not yet recruiting
      • Raigmore Hospital
• United States
  • Alabama
    • Alexander City, Alabama, United States, 35010
      • Recruiting
      • Advanced Cariodvascular LLC
    • Fairhope, Alabama, United States, 36532
      • Recruiting
      • Eastern Shore Rsrch Inst, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Not yet recruiting
      • Cardiology & Medicine Clinic
  • California
    • Northridge, California, United States, 91325
      • Not yet recruiting
      • Valley Clinical Trials, Inc.
    • Orange, California, United States, 92868
      • Not yet recruiting
      • UCI Health
    • Pasadena, California, United States, 91105
      • Not yet recruiting
      • South California Heart Spc
  • Florida
    • Largo, Florida, United States, 33777
      • Not yet recruiting
      • Clearwater Cardiovascular Consultants
    • Ormond Beach, Florida, United States, 32174
      • Recruiting
      • Ormond Beach Clinical Research
    • Saint Augustine, Florida, United States, 32086
      • Recruiting
      • St Johns Ctr Clin Rsch-St. Aug
  • Georgia
    • Macon, Georgia, United States, 31201
      • Not yet recruiting
      • GA Arrhythmia Cons & Rsch Inst
    • Savannah, Georgia, United States, 31406
      • Not yet recruiting
      • Velocity Clin Rsrch - Savannah
  • Illinois
    • Hazel Crest, Illinois, United States, 60429
      • Recruiting
      • Chicago Medical Research LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Not yet recruiting
      • UofL Health Care Outpatient
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Recruiting
      • Maryland Cardiovascular Specialists - Baltimore
    • Oxon Hill, Maryland, United States, 20745
      • Not yet recruiting
      • MD Medical Research
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48304
      • Not yet recruiting
      • Cardio and Vascular Assoc-CAVA
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Not yet recruiting
      • Kansas City VA Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University
  • Nevada
    • Reno, Nevada, United States, 89502
      • Not yet recruiting
      • Renown Children's Hospital
  • New York
    • Lake Success, New York, United States, 11042
      • Not yet recruiting
      • Long Island Cardiovascular Consultants PC
    • New York, New York, United States, 10019
      • Not yet recruiting
      • Mount Sinai Hosp at NYC
    • Riverhead, New York, United States, 11901
      • Not yet recruiting
      • Northwell Health Phys Cardio
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7046
      • Not yet recruiting
      • University of North Carolina at Chapel Hill
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Not yet recruiting
      • AMS Cardiology
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • University of Pennsylvania Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Not yet recruiting
      • PharmaTex Research
    • Dallas, Texas, United States, 75390-9302
      • Not yet recruiting
      • University of Texas Southwestern Medical Center
    • El Paso, Texas, United States, 79905
      • Recruiting
      • David Turbay, MD, PLLC
    • Katy, Texas, United States, 77493
      • Not yet recruiting
      • Private Practice Leadership LLC.
    • San Antonio, Texas, United States, 78212
      • Not yet recruiting
      • Clinical Advancement Ctr, PLLC
    • Sherman, Texas, United States, 75092
      • Not yet recruiting
      • Sherman Clinical Research
    • Tomball, Texas, United States, 77375
      • Not yet recruiting
      • Northwest Heart Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Withdrawn
      • Sentara Clinical Research
    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 centimeter (cm)
  3. LA length greater than or equal to 5.0 cm
  4. LA area greater than or equal to 20 square centimeter (cm^2)
  5. LA volume greater than or equal to 55 milliliter (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 gram 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 centimeter 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ziltivekimab; Participants will receive ziltivekimab administered subcutaneously (s.c.) once-monthly and added to standard of care for 12 months.	Drug: Ziltivekimab; Zilitivekimab will be administered subcutaneously once-monthly.
Placebo Comparator: Placebo; Participants will receive placebo matched to ziltivekimab administered s.c. once-monthly and added to standard of care for 12 months.	Drug: Placebo; Placebo matched to ziltivekimab will be administered subcutaneously once-monthly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (KCCQ-CSS)	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.	From randomisation (month 0) to end-of-treatment (month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant achieving threshold for clinically meaningful within-participant change in KCCQ CSS (yes/no)	Measured as count of participants. 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.	From randomisation (month 0) to end-of-treatment (month 12)
Participant achieving threshold for clinically meaningful within-participant change in 6-minute walk distance (6MWD) (yes/no)	Measured as count of participants.	From randomisation (month 0) to end-of-treatment (month 12)
Participants improving 5 points or more in KCCQ-CSS (yes/no)	Measured as count of participants. 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.	From randomisation (month 0) to end-of-treatment (month 12)
Participants improving 10 points or more in KCCQ-CSS (yes/no)	Measured as count of participants. 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.	From randomisation (month 0) to end-of-treatment (month 12)
Change in subscales of KCCQ (total symptom score, physical limitations score, social limitations score, and health-related quality of life)	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.	From randomisation (month 0) to end-of-treatment (month 12)
Change in six-minute walk distance (6MWD)	Measured in meters.	From randomisation (month 0) to end-of-treatment (month 12)
Change in high-sensitivity C-reactive protein (hs-CRP)	Measured as ratio to baseline.	From randomisation (month 0) to end-of-treatment (month 12)
Participants experiencing improvement in New York heart association (NYHA) Class (yes/no)	Measured as count of participants. The New York Heart Association (NYHA) classification provides a simple way of classifying the extent of heart failure (HF). It classifies patients in one of four categories based on their limitations during physical activity - Class I: Participant with cardiac disease but without resulting limitations of physical activity, Class II: Participants with cardiac disease resulting in slight limitation of physical activity, Class III: Participants with cardiac disease resulting in marked limitation of physical activity, Class IV: Participants with cardiac disease resulting in inability to carry on any physical activity without discomfort.	From randomisation (month 0) to end-of-treatment (month 12)
Change in N-terminal-pro-brain natriuretic peptide (NT-proBNP)	Measured as ratio to baseline.	From randomisation (month 0) to end-of-treatment (month 12)
Change in eGFR (CKD-EPI)	eGFR (CKD-EPI) is estimated glomerular filtration rate chronic kidney disease - epidemiology collaboration. Measured in milliliter per minute per 1.73 square meter (ml/min/1.73^2).	From randomisation (month 0) to end-of-treatment (month 12)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): May 13, 2026
• Study Completion (Estimated): August 17, 2026

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Failure; Inflammation
• Other Study ID Numbers: NN6018-4914; U1111-1293-7516 (Other Identifier: World Health Organisation (WHO)); 2023-506988-34 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No