ATHENA: A research study looking into how ziltivekimab works compared to placebo in people with heart failure and inflammation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Mar 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-506988-34-00

WHO UTN

U1111-1293-7516

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate superiority of ziltivekimab s.c. once-monthly versus placebo, both added to standard of care, on heart failure symptoms and physical function in participants with HFmrEF or HFpEF, and systemic inflammation

Secondary objectives 1

1. To compare the effects of ziltivekimab s.c. once monthly versus placebo, both added to standard of care, on biomarkers of inflammation and heart failure symptoms, progression of CKD and physical limitations in participants with HFmrEF or HFpEF, and systemic inflammation.

Conditions and MedDRA coding

Heart failure with mildly reduced or preserved ejection fraction and systemic inflammation

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Medicines And Healthcare Products Regulatory Agency

EMA paediatric investigation plan (PIP)

EMEA-002840-PIP02-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Serum hs-CRP 2 mg/L at screening (visit 1).
2. NT-proBNP ≥ 225 pg/mL (375 pg/mL for patients with atrial fibrillation/flutter) at screening.
3. Diagnosis of heart failure (NYHA Class II-III).
4. LVEF > 40% 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. MI or HF hospitalisation).
5. 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: a) LA volume index > 34mL/m2 b) LA diameter ≥ 3.8cm c) LA length ≥ 5.0cm d) LA area ≥ 20cm2 e) LA volume ≥ 55mL f) Intraventricular septal thickness ≥ 1.1cm g) Posterior wall thickness ≥ 1.1cm h) LV mass index ≥ 115g∕m2 in men or ≥ 95 g∕m2 in women i) E/e’ (mean septal and lateral) ≥ 10 j) e’ (mean septal and lateral) < 9cm/s
6. No heart failure hospitalisations or urgent heart failure visits between screening and randomisation.
7. Able to perform the 6MWT at screening with a minimum distance of 100 metres. (NOTE: Patients are not eligible if any disease or condition, rather than HF, constitutes the main reason for limiting the ability to exercise/reduces exercise capacity).
8. KCCQ clinical summary score < 80 at screening

Exclusion criteria 10

1. Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation within 30 days prior to screening (visit 1).
2. Systolic blood pressure ≥180 mmHg at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving ≥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).
3. Heart rate above 110 or below 40 beats per minute as evaluated on the 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).
4. Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (NOTE: Planned coronary angiogram is not exclusionary).
5. Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
6. 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).
7. 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.
8. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
9. Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
10. Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary: Change in KCCQ clinical summary score (KCCQ-CSS) from randomisation (month 0) to end-of-treatment (month 12) (Score (score on scale; range; 0-100))

Secondary endpoints 15

1. Confirmatory secondary: Change in six-minute walk distance (6MWD) from randomisation (month 0) to end-of-treatment (month 12) (Metres)
2. Supportive secondary: Change in hs-CRP from randomisation (month 0) to end-of-treatment (month 12) (Ratio to baseline)
3. Supportive secondary: Participants experiencing improvement in NYHA Class (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participant)
4. Supportive secondary: Change in NT-proBNP from randomisation (month 0) to end-of-treatment (month 12) (Ratio to baseline)
5. Supportive secondary: Change in eGFR (CKD-EPI) from randomisation (month 0) to end-of-treatment (month 12) (mL/min/1.73 m2)
6. Supportive secondary: Participants achieving threshold for meaningful within- patient change in KCCQ-CSS (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participants)
7. Supportive secondary: Participants achieving threshold for meaningful within- patient change in 6MWD (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participants)
8. Supportive secondary: Participants improving 5 points or more in KCCQ-CSS (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participants)
9. Supportive secondary: Participants improving 10 points or more in KCCQ-CSS (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participants)
10. Supportive secondary: Change in KCCQ overall summary score (KCCQ-CCS) from randomisation (month 0) to end-of-treatment (month 12) (Score (score on scale; range 0-100))
11. Supportive secondary: Participants experiencing deterioration in NYHA class (yes/no) from randomisation (month 0) to end-of-treatment (month 12) (Count of participants)
12. Supportive secondary: Change in KCCQ total symptom score from randomisation (month 0) to end-of-treatment (month 12) (Score, range 0-100)
13. Supportive secondary: Change in KCCQ physical limitations score from baseline (month 0) to end-of-treatment (month 12) (Score, range 0-100)
14. Supportive secondary: Change in KCCQ social limitations score from randomisation (month 0) to end-of-treatment (month 12) (Score, range 0-100)
15. Supportive secondary: Change in KCCQ health-related quality of life score from randomisation (month 0) to end-of-treatment (month 12) (Score, range 0-100)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 7

Locations

7 EU/EEA countries · 67 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 135 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications