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

Heart Failure Clinical Trial

— ATHENA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06200207
• Other study ID #: NN6018-4914
• Secondary ID: U1111-1293-75162
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: August 17, 2026

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 680
• Est. completion date: August 17, 2026
• Est. primary completion date: May 13, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Inflammation
• Systemic Inflammation

Intervention

Drug:
• Ziltivekimab
Zilitivekimab will be administered subcutaneously once-monthly.
• Placebo
Placebo matched to ziltivekimab will be administered subcutaneously once-monthly.

Locations

Country	Name	City	State
Argentina	Centro Medico Dra. Laura Maffei e Investigacion Clínica Apli	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes SRL	Buenos Aires
Argentina	Centro de Investigación y Prevención Cardiovascular	Caba
Argentina	Centro Médico CIMEL	Lanus Este	Buenos Aires
Argentina	Consultorio Integral de Atención al Diabético	Morón
Argentina	Centro Cardiovascular Salta	Salta
Argentina	Investigaciones Clinicas Tucuman	San Miguel De Tucumán, Tucumán.
Australia	Ballarat Base Hospital	Ballarat	Victoria
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	The Cardiologists Pty Ltd	Epping	Victoria
Australia	The Cardiologists Pty Ltd	Epping	Victoria
Australia	Fiona Stanley Hospital Cardiology	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Illawarra Heart Health Centre	Wollongong	New South Wales
Bulgaria	MHAT Haskovo AD	Haskovo
Bulgaria	UMHAT Heart and Brain	Pleven
Bulgaria	"UMHAT "Sveti Georgi" EAD	Plovdiv
Bulgaria	"Medical Center Hera" EOOD - Sofia	Sofia
Bulgaria	"UMHAT "Sveta Anna" Sofia" AD, Clinic of Cardiology	Sofia
Bulgaria	"UMHATEM N.I. Pirogov" EAD	Sofia
Bulgaria	Medico-dental center ISUL - Tsaritsa Yoanna EOOD	Sofia
Canada	University of Calgary_Calgary	Calgary	Alberta
Canada	Cambridge Cardiac Care Centre	Cambridge	Ontario
Canada	Saul Vizel Pro. Med. Corp	Cambridge	Ontario
Canada	Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	CHU de Quebec-Uni Laval-Hotel	Quebec
Canada	Corcare Cardiovascular Research	Scarborough	Ontario
Canada	Diabetes Heart Research Centre	Toronto	Ontario
Canada	Clinical Research Solutions Inc.	Waterloo	Ontario
Canada	CPS Research	Waterloo	Ontario
Czechia	Kardiologicka ambulance Brno s.r.o.	Brno
Czechia	Vojenska nemocnice Brno	Brno
Czechia	Poliklinika Holešovice VISIONARY - MEDICON a.s.	Praha 7
Czechia	Svitavska nemocnice Kardiologie	Svitavy
Czechia	Kardiologie Trutnov Ferkl	Trutnov
France	Centre Hospitalier Regional Universitaire de Tours-Hopital Trousseau	Chambray Les Tours
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
France	Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou	Rennes
France	Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle	Rouen cedex
France	Centre Hospitalier Intercommunal Toulon La Seine-Sur-Mer - Hopital Sainte Musse	Toulon
France	Chru de Nancy - Hopital Brabois	Vandoeuvre Les Nancy
Germany	Herzzentrum Dresden GmbH Universitätsklinik	Dresden
Germany	Zentrum fuer klinische Studien Suedbrandenburg GmbH	Elsterwerda
Germany	MVZ CCB Frankfurt Und Main-Taunus GbR	Frankfurt
Germany	Medical Center - University Of Freiburg	Freiburg
Germany	UKS - Innere Medizin III	Homburg
Germany	Kardiopraxis Schirmer	Kaiserslautern
Greece	"Hygeia" General Hospital of Athens	Athens
Greece	'G. Gennimatas' General Hospital of Athens	Athens
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens	Attiki
Greece	Evangelismos Hospital	Athens
Greece	Konstantopouleio G.H. of Athens, "Agia Olga"	Athens
Greece	U.G.H of Athens "Attikon"	Chaidari, Athens
Greece	General Hospital of Chios "Skilitsio"	Chios
Greece	Univ Gen Hospital Larisa, Cardiology Medicine Clinic	Larissa
Greece	Sismanogleio General Hospital	Marousi
Greece	"AHEPA" University General Hospital of Thessaloniki	Thessaloniki
Greece	'Ippokrateio' General Hospital of Thessaloniki	Thessaloniki
Greece	Gen Hospital of Thessaloniki G.Papanikolaou,Cardiology Dpt	Thessaloniki
India	KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre	Belagavi	Karnataka
India	Sri Jayadeva Institute of Cardiovascular Sciences & Research	Bengaluru	Karnataka
India	St John's Medical College Hospital	Bengaluru	Karnataka
India	All India Institute of Medical Sciences (AIIMS), Bhubaneswar	Bhubaneswar	Odisha
India	Jawaharlal Nehru Medical College and Hospital	Bikaner	Rajasthan
India	S.P. Medical College & Associated Group of Hospitals	Bikaner	Rajasthan
India	Guru Nanak CARE Hospitals	Hyderabad	Telangana
India	Malla Reddy Narayana Multispeciality Hospital	Hyderabad	Telangana
India	Ganesh Shankar Vidyarthe Memorial Medical College (GSVM Medical College)	Kanpur	Uttar Pradesh
India	B M Birla Heart Research Centre	Kolkata	West Bengal
India	Dr. Ram Manohar Lohia Institute of Medical Sciences	Lucknow	Uttar Pradesh
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences	Lucknow	Uttar Pradesh
India	Manipal Hospital, Mysuru	Mysuru	Karnataka
India	All India Institute of Medical Sciences (AIIMS), Nagpur	Nagpur	Maharashtra
India	Sengupta Hospital and Research Institute	Nagpur	Maharashtra
India	Chopda Medicare and Research Centre Pvt. Ltd.	Nashik	Maharashtra
India	Vijan Hospital & Research Centre	Nashik	Maharashtra
India	Vijan Hospital & Research Centre	Nashik	Maharashtra
India	All India Institute of Medical Sciences (AIIMS)	New Delhi	Delhi
India	G B Pant Institute of Postgraduate Medical Education and Research	New Delhi	Delhi
India	Rajiv Gandhi Super Speciality Hospital	New Delhi	Delhi
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Vardhaman Mahavir Medical College & Safdarjung Hospital	New Delhi	Delhi
India	Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)	Puducherry
India	Villoo Poonawalla Memorial Hospital	Pune	Maharashtra
India	Kasturba Medical College and Hospital, Manipal	Udupi	Karnataka
India	Rhythm Heart Institute	Vadodara	Gujarat
India	Siddhartha Medical College & Government General Hospital	Vijaywada	Andhra Pradesh
India	King George Hospital	Visakhapatnam	Andra Pradesh
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Hospital Raja Permaisuri Bainun Ipoh	Ipoh	Perak
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Hospital Serdang	Kajang
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu, Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	10 Wojskowy Szpital Kliniczny z Poliklinika - Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Bydgoszczy	Bydgoszcz
Poland	Centrum Medyczne Intercor Sp. z o.o.	Bydgoszcz	Kujawsko-Pomorskie
Poland	Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman	Gdynia
Poland	Szpitale Pomorskie Sp. z o.o.	Gdynia
Poland	Szpitale Pomorskie Sp. z o.o.	Gdynia	Pomorskie
Poland	Pratia S.A.	Jelenia Góra	Dolnoslaskie
Poland	Cardiomedicum Sp. z o.o.	Kraków	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny Im Wojskowej Akademii Medycznej Centralny Szpital Weteranow	Lodz	Lodzkie
Poland	Formed 2 Sp. z o.o.	Oswiecim	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny W Poznaniu	Poznan
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Pulawach	Pulawy	Lubelskie
Poland	Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji	Warszawa
Portugal	CHTâmega e Sousa - Hospital Padre Américo	Guilhufe - Penafiel
Portugal	Centro Hospitalar Lisboa Norte	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	CHLO, EPE - Hospital São Francisco Xavier	Lisbon
Portugal	Centro Hospitalar de Setubal	Setubal
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca	Castilla Y León
Spain	Hospital Virgen del Camino - Sanlúcar de Barrameda	Sanlúcar de Barrameda
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Clínica Nuevas Tecnologías en Diabetes y Endocrinología	Sevilla
Spain	Hospital Nisa Sevilla Aljarafe	Sevilla
Spain	Fundación para la Investigación del Hospital Clínico de Valencia (INCLIVA)	Valencia
Turkey	T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastan	Adana
Turkey	Afyonkarahisar Health Sciences University	Afyon
Turkey	Ankara Sehir Hastanesi Cardiology	Ankara
Turkey	Bursa Sehir Hastanesi Cardiology	Bursa
Turkey	Trakya University	Edirne
Turkey	Basaksehir Cam ve Sakura Sehir Hastanesi	Istanbul
Turkey	Erciyes University Cardiology	Kayseri
Turkey	Kocaeli Universitesi Tip Fakultesi Hastanesi	Kocaeli
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Raigmore Hospital	Inverness	Highland
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	St. Richards Hospital	West Sussex
United States	Advanced Cariodvascular LLC	Alexander City	Alabama
United States	PharmaTex Research	Amarillo	Texas
United States	Maryland Cardiovascular Specialists - Baltimore	Baltimore	Maryland
United States	Cardio and Vascular Assoc-CAVA	Bloomfield Hills	Michigan
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	David Turbay, MD, PLLC	El Paso	Texas
United States	Eastern Shore Rsrch Inst, LLC	Fairhope	Alabama
United States	Chicago Medical Research LLC	Hazel Crest	Illinois
United States	AMS Cardiology	Horsham	Pennsylvania
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	Private Practice Leadership LLC.	Katy	Texas
United States	Long Island Cardiovascular Consultants PC	Lake Success	New York
United States	Clearwater Cardiovascular Consultants	Largo	Florida
United States	Cardiology & Medicine Clinic	Little Rock	Arkansas
United States	UofL Health Care Outpatient	Louisville	Kentucky
United States	GA Arrhythmia Cons & Rsch Inst	Macon	Georgia
United States	Mount Sinai Hosp at NYC	New York	New York
United States	Sentara Clinical Research	Norfolk	Virginia
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	UCI Health	Orange	California
United States	Ormond Beach Clinical Research	Ormond Beach	Florida
United States	MD Medical Research	Oxon Hill	Maryland
United States	South California Heart Spc	Pasadena	California
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Renown Children's Hospital	Reno	Nevada
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Northwell Health Phys Cardio	Riverhead	New York
United States	St Johns Ctr Clin Rsch-St. Aug	Saint Augustine	Florida
United States	Washington University	Saint Louis	Missouri
United States	Clinical Advancement Ctr, PLLC	San Antonio	Texas
United States	Clinical Advancement Ctr, PLLC	San Antonio	Texas
United States	Velocity Clin Rsrch - Savannah	Savannah	Georgia
United States	Sherman Clinical Research	Sherman	Texas
United States	Northwest Heart Center	Tomball	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  India,  Malaysia,  Poland,  Portugal,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Change in six-minute walk distance (6MWD)	Measured in meters.	From randomisation (month 0) to end-of-treatment (month 12)
Secondary	Change in high-sensitivity C-reactive protein (hs-CRP)	Measured as ratio to baseline.	From randomisation (month 0) to end-of-treatment (month 12)
Secondary	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)
Secondary	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)
Secondary	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)