A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation

NCT05636176
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
4,899
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Lead sponsor
Novo Nordisk A/S
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Start date
2023-05-08
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Number of sites
1,013
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Summary
This study will be done to see if ziltivekimab can be used to treat people living with heart failure and inflammation. Participants will either get ziltivekimab or placebo. Participants will get study medicine for once-monthly injections either in a pre-filled syringe to inject the study medicine into a skinfold or a pen-injector to inject the study medicine into flat skin. The study is expected to last for up to 4 years. Participants will have up to 20 clinic visits. Participants will have to use a study app on their phone to record and share information about all their injections of study medicine and to fill in questionnaires.
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Acronym
HERMES
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Short title
A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation
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Official title
Effects of Ziltivekimab Versus Placebo on Morbidity and Mortality in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Systemic Inflammation
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2027-07-02
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First posted
2022-12-05
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Registry last updated
2026-08-12
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Primary completion date
2027-07-02
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Start date
2023-05-08
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Actual participants
4,899
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Participants
4,899
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
1,013
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Novo Nordisk A/S
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05636176
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ClinicalTrials.gov ID
NCT05636176
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Time to First Occurrence of a Composite Heart Failure Endpoint Consisting of: Cardiovascular (CV) Death, Heart Failure (HF) Hospitalisation or Urgent HF Visit

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  1. Time to First Occurrence of 4-point Expanded Composite HF Endpoint, a Composite Endpoint Consisting of: CV Death, HF Hospitalisation or Urgent HF Visit, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  2. Number of CV Deaths, HF Hospitalisations or Urgent HF Visits (First and Recurrent)

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured as count of event.

  3. Time to Occurrence of CV Death

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  4. Time to Occurrence of all-cause Death

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  5. Time to First Occurrence of 4-point Expanded Composite HF Endpoint, a Composite Endpoint Consisting of: All-cause Death, HF Hospitalisation or Urgent HF Visit, Non-fatal MI, Non-fatal stroke

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  6. Hierarchical Composite of: Time to All-cause Death, Number of HF Hospitalisations or Urgent HF Visits, Time to First HF Hospitalisation or Urgent HF Visit, difference of at least 5 in KCCQ clinical summary score change from baseline to 12 months

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Kansas City Cardiomyopathy Questionnaire (KCCQ) measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. Score ranges from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health related quality of life, respectively. Measured as total wins for each treatment group.

  7. Time to First Occurrence of HF Hospitalisation or Urgent HF Visit

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured in months.

  8. Number of Events of Atrial Fibrillation

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured as count of event.

  9. Change in KCCQ Clinical Summary Score

    Timeframe: From randomisation (month 0) to 12 months

    KCCQ measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. Score ranges from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health related quality of life, respectively. Measured as score.

  10. Improvement of 5 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Timeframe: From randomisation (month 0) to 12 months

    Kansas City Cardiomyopathy Questionnaire (KCCQ) measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. Score ranges from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health related quality of life, respectively. Measured as count of participant.

  11. Improvement of 10 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Timeframe: From randomisation (month 0) to 12 months

    Kansas City Cardiomyopathy Questionnaire (KCCQ) measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. Score ranges from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health related quality of life, respectively. Measured as count of participant.

  12. Improvement in New York Heart Association (Classification) [NYHA Class] (Yes/No)

    Timeframe: From randomisation (month 0) to 12 months

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) 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. Measured as count of participant.

  13. Time to First Occurrence of a Composite Chronic Kidney Disease (CKD) Endpoint Consisting of: CV death, Onset of Persistent Greater Than Equal To 40 Percentage Reduction in eGFR (CKD- EPI) compared with baseline; Kidney failure

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    eGFR = estimated glomerular filtration rate; CKD-EPI = chronic kidney disease - epidemiology collaboration. Kidney failure defined as: death from kidney failure, onset of persistent eGFR less than 15 milliliters per minute (mL/min)/1.73 meter square (m\^2) (CKD-EPI), initiation of chronic kidney replacement therapy (maintenance dialysis or kidney transplantation). Measured in months.

  14. Change in Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease - Epidemiology Collaboration [CKD-EPI])

    Timeframe: From randomisation (month 0) to 12 months

    Measured as mL/min/1.73 m\^2.

  15. Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured as mL/min/1.73 m\^2/year.

  16. Number of Hospitalisations With Infection as Primary Cause or Death Due to Infection

    Timeframe: From randomisation (month 0) to end of study (up to 48 months)

    Measured as count of event.

  17. Change in High-sensitivity C-reactive Protein (hs-CRP)

    Timeframe: From randomisation (month 0) to 12 months

    Measured as ratio to baseline.

  18. Change in N-terminal-pro-brain Natriuretic Peptide (NT-proBNP)

    Timeframe: From randomisation (month 0) to 12 months

    Measured as ratio to baseline.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2 milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular

  • At least one of the following:

    1. N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
    2. Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL.

  • Diagnosis of heart failure (New York Heart Association [classification] [NYHA] Class II-IV).

  • Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) 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 (e.g., 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:

  • Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m^2).

  • LA diameter greater than equal to 3.8 centimeter (cm).

  • LA length greater than equal to 5.0 cm.

  • LA area greater than equal to 20 cm square.

  • LA volume greater than equal to 55 milliters (mL).

  • Intraventricular septal thickness greater than equal to 1.1 cm.

  • Posterior wall thickness greater than equal to 1.1 cm.

  • Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m^2 ) in men or greater than equal to 95 g⁄m^2 in women.

  • E/e' (mean septal and lateral) greater than equal to 10.

  • e' (mean septal and lateral) less than 9 centimeter per second (cm/s).

  • No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).

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 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 equal to 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
  • Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram (ECG) performed at screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
  • Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).
  • 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 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.

Sources for eligibility
clinicaltrials.gov

  • Advanced Cardiovascular, LLCAlexander City, United States
  • Eastern Shore Rsrch Inst, LLCFairhope, United States
  • Heart Center Rsrch_HunstvilleHuntsville, United States
  • Banner University Medical CtrPhoenix, United States
  • Cardiology & Medicine ClinicLittle Rock, United States
  • InvivoCure -2Alhambra, United States
  • National Heart Institute CalBeverly Hills, United States
  • Valley Clinical TrialsCovina, United States
  • Scripps Memorial Hospital La JollaLa Jolla, United States
  • Purushotham & Akther Kotha MD, inc.La Mesa, United States
  • VA Loma Linda Hlthcr SysLoma Linda, United States
  • Biopharma Clinical Research Services, LLCLos Angeles, United States
  • VA Greater Los Angeles Hlthcare SystemLos Angeles, United States
  • VAGrtrLosAngelesHlthcareSystemLos Angeles, United States
  • Valley Clinical Trials, Inc.Northridge, United States
  • UCI HealthOrange, United States
  • Stanford Univ School of MedPalo Alto, United States
  • San Diego Cardiac CenterSan Diego, United States
  • North America Research InstituteSan Dimas, United States
  • Manshadi Heart InstituteStockton, United States
  • Lundquist Inst-Biomed InnovtnTorrance, United States
  • InvivoCureVan Nuys, United States
  • Rocky Mountain Regional VAMCAurora, United States
  • InvivoCure -2Denver, United States
  • S Denver Cardiology AssociatesLittleton, United States

And 988 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • jRCT2031230085
  • 2022-501939-16-00
  • U1111-1280-0810
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)

Targets (1)