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

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ClinicalTrials.gov Identifier: NCT06200207
Recruitment Status : Recruiting
First Posted : January 10, 2024
Last Update Posted : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Heart Failure Systemic Inflammation Drug: Ziltivekimab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 680 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 1, 2024
Estimated Primary Completion Date : May 13, 2026
Estimated Study Completion Date : August 17, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (KCCQ-CSS) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Participant achieving threshold for clinically meaningful within-participant change in KCCQ CSS (yes/no) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    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.

  2. Participant achieving threshold for clinically meaningful within-participant change in 6-minute walk distance (6MWD) (yes/no) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    Measured as count of participants.

  3. Participants improving 5 points or more in KCCQ-CSS (yes/no) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    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.

  4. Participants improving 10 points or more in KCCQ-CSS (yes/no) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    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.

  5. Change in subscales of KCCQ (total symptom score, physical limitations score, social limitations score, and health-related quality of life) [ Time Frame: 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.

  6. Change in six-minute walk distance (6MWD) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    Measured in meters.

  7. Change in high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    Measured as ratio to baseline.

  8. Participants experiencing improvement in New York heart association (NYHA) Class (yes/no) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    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.

  9. Change in N-terminal-pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    Measured as ratio to baseline.

  10. Change in eGFR (CKD-EPI) [ Time Frame: From randomisation (month 0) to end-of-treatment (month 12) ]
    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).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06200207


Contacts
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Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Transparency dept. 2834 Novo Nordisk A/S
More Information
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT06200207    
Other Study ID Numbers: NN6018-4914
U1111-1293-7516 ( Other Identifier: World Health Organisation (WHO) )
2023-506988-34 ( Other Identifier: European Medical Agency (EMA) )
First Posted: January 10, 2024    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Inflammation
Heart Diseases
Cardiovascular Diseases
Pathologic Processes