Condition médicale (spécialité visée)
Choix aire thérapeutique
Cardiologie et maladies vasculaires
Stades de cancer
Non applicable
Biomarqueur
Non applicable
Profil des participants
Sexe(s) des participants
TOUS
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion :
* Protéine C-réactive à haute sensibilité (hs-CRP) supérieure ou égale à 2 milligrammes par litre (mg/L) lors du dépistage (visite 1) Spécifique à la maladie - cardiovasculaire
* Au moins l'un des suivants :
1. Peptide natriurétique pro-cérébral N-terminal (NT-proBNP) supérieur ou égal à 300 picogrammes par millilitre (pg/mL) lors du dépistage (visite 1) pour les patients sans fibrillation/flutter auriculaire en cours. Si fibrillation/flutter auriculaire en cours lors du dépistage (visite 1), le NTproBNP doit être supérieur ou égal à 600 pg/mL. Notez que l'électrocardiogramme de dépistage (ECG) doit être obtenu le même jour que l'échantillonnage pour le NT-proBNP.
2. Hospitalisation ou visite urgente/non planifiée avec un diagnostic principal d'insuffisance cardiaque décompensée nécessitant un traitement diurétique en boucle intraveineux, au cours des 9 derniers mois avant le dépistage (visite 1) en combinaison avec un NT-proBNP supérieur ou égal à 200 pg/mL lors du dépistage (visite 1) pour les patients sans fibrillation/flutter auriculaire en cours. Si fibrillation/flutter auriculaire en cours lors du dépistage (visite 1), NT-proBNP doit être supérieur ou égal à 600 pg/mL.
* Diagnostic d'insuffisance cardiaque (classification de l'Association cardiaque de New York [NYHA] classe II-IV).
* Fraction d'éjection ventriculaire gauche (FEVG) supérieure à 40 pourcentage (%) documentée par échocardiographie dans les 12 mois précédant ou lors du dépistage (visite 1). La FEVG doit être documentée dans les dossiers médicaux et la mesure la plus récente doit être utilisée pour déterminer l'admissibilité sans événement intermédiaire signalant une détérioration potentielle de la fraction d'éjection (par exemple, infarctus du myocarde [IM] ou hospitalisation pour insuffisance cardiaque [HF]).
* Maladie cardiaque structurelle et/ou fonctionnelle documentée par échocardiographie dans les 12 mois précédant ou lors du dépistage (visite 1) montrant au moins l'un des suivants :
* Indice de volume de l'oreillette gauche (LA) supérieur à 34 millilitres par mètre carré (mL/m^2).
* Diamètre de l'oreillette gauche supérieur ou égal à 3,8 centimètre (cm).
* Longueur de l'oreillette gauche supérieure ou égale à 5,0 cm.
* Surface de l'oreillette gauche supérieure ou égale à 20 cm carrés.
* Volume de l'oreillette gauche supérieur ou égal à 55 millilitres (mL).
* Épaisseur du septum interventriculaire supérieure ou égale à 1,1 cm.
* Épaisseur de la paroi postérieure supérieure ou égale à 1,1 cm.
* Indice de masse ventriculaire gauche (LV) supérieur ou égal à 115 grammes par mètre carré (g⁄m^2) chez les hommes ou supérieur ou égal à 95 g⁄m^2 chez les femmes.
* E/e' (moyenne septale et latérale) supérieure ou égale à 10.
* e' (moyenne septale et latérale) inférieure à 9 centimètres par seconde (cm/s).
* Aucune hospitalisation pour insuffisance cardiaque ou visite urgente pour insuffisance cardiaque entre le dépistage (visite 1) et la randomisation (visite 2).
Critères d'exclusion :
Conditions médicales - cardiovasculaires
* Infarctus du myocarde, accident vasculaire cérébral, angine de poitrine instable, attaque ischémique transitoire, ou hospitalisation pour insuffisance cardiaque, dans les 30 jours précédant le dépistage (visite 1).
* Pression artérielle systolique supérieure ou égale à 180 millimètres de mercure (mmHg) lors du dépistage (visite 1). Si la pression artérielle systolique est de 160-179 mmHg, le patient doit recevoir plus de 3 médicaments antihypertenseurs. (Remarque : les participants potentiels peuvent être retestés pour ce critère dans la fenêtre de visite et sans nouveau dépistage, à la discrétion de l'investigateur).
* Fréquence cardiaque supérieure à 110 ou inférieure à 40 battements par minute évaluée sur l'électrocardiogramme (ECG) réalisé lors du dépistage (visite 1) (Remarque : les participants potentiels peuvent être retestés pour ce critère dans la fenêtre de visite et sans nouveau dépistage, à la discrétion de l'investigateur).
* Revascularisation coronarienne, carotidienne ou périphérique planifiée connue pendant la période de dépistage (visite 1). (Remarque : l'angiogramme coronarien planifié n'est pas exclu).
* Dispositif cardiaque planifié ou procédure d'ablation de flutter/atrial fibrillation planifiée connue pendant la période de dépistage (visite 1).
* Intervention chirurgicale cardiaque majeure, chirurgie non cardiaque majeure, ou procédure endoscopique majeure (thoracoscopique ou laparoscopique) au cours des 60 jours précédant la randomisation (visite 2) ou toute intervention chirurgicale majeure planifiée au moment de la randomisation (visite 2).
* Insuffisance cardiaque due à une cardiomyopathie infiltrante (par exemple, sarcoidose, amyloïde), cardiomyopathie ventriculaire droite arythmogène, cardiomyopathie de Takutsubo, cardiomyopathie hypertrophique génétique ou cardiomyopathie obstructive, myocardite active, péricardite constrictive, tamponnade cardiaque, maladie valvulaire primaire non corrigée plus que modérée.
* Hypertension pulmonaire primaire, embolie pulmonaire chronique, maladie pulmonaire sévère incluant la BPCO.
* Toute autre condition jugée par l'investigateur pouvant expliquer les symptômes et signes d'insuffisance cardiaque (par exemple, anémie, hypothyroïdie).
Conditions médicales - infections/immunosuppression
- Preuve clinique de, ou suspicion d'infection active à la discrétion de l'investigateur.
Inclusion Criteria:
* 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).
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 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.
Critères d'exclusion
1. Known or suspected hypersensitivity to study intervention or related products.
2. Previous randomisation in this study.
3. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method, as defined in Appendix 4 (Section 10.4.2).
4. Participation (i.e., signed informed consent) in any other interventional clinical study of an approved or non-approved investigational medicinal product within 30 days prior to screening (visit 1).
5. Participation in any clinical study of an approved or non-approved device for the treatment of heart failure within 30 days prior to screening (visit 1).
6. Any disorder, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
7. Inadequate standard of care treatment which in the investigator’s opinion makes participation in the study inappropriate.
8. Unstable medical therapy for heart failure (including dose of diuretics) within 14 days prior to screening visit (visit 1) (at the discretion of the investigator).
9. Absolute neutrophil count <2×109/L at screening (visit 1).
10. Platelet count <120×109/L at screening (visit 1).
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of normal at screening (visit 1).
12. Active hepatitis C (positive anti-HCV and detectable HCV RNA) or hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) at screening (visit 1). (Note: Participants with positive anti-HBc and undetectable HBV DNA can be enrolled).
13. Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation within 30 days prior to screening (visit 1).
14. 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).
15. 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).
16. Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: planned coronary angiogram is not exclusionary).
17. Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
18. 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).
19. Left Ventricular Assist Device (LVAD) implantation or heart transplantation
20. 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.
21. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
22. Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
23. Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
24. History of recurrent serious infections (infections leading to hospitalisation or use of i.v. antibiotics) in the 12 months prior to randomisation (visit 2), at the discretion of the investigator.
25. Diagnosis of human immunodeficiency virus (HIV) and not receiving a stable antiretroviral regimen, at the discretion of the investigator at screening (visit 1).
26. History or evidence of untreated latent tuberculosis (TB) such as (but not limited to):
• History of a positive TB test or chest X-ray compatible with latent TB; and TB treatment initiated less than 28 days prior to randomisation (visit 2).
Confirmed positive for latent TB at screening (visit 1) and TB treatment initiated less than 28 days prior to randomisation (visit 2).
27. eGFR<15 mL/min/1.73 m2 (CKD-EPI9) at screening (visit 1)a or chronic haemodialysis or peritoneal dialysis.
28. History of gastrointestinal perforation. (Note: History of perforated appendicitis more than 5 years prior to screening (visit 1) is not exclusionary).
29. History of active diverticulitis in the 5 years prior to randomisation (visit 2).
30. History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomisation (visit 2).
31. Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low risk prostate cancer, or in-situ carcinomas of the cervix, or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years prior to screening (visit 1).
32. History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the study. Note: Patients no longer receiving immune suppressant therapy and who are in full remission following bone marrow transplant can be included in the study.
Prior or current medication
33. Received a live or attenuated-live vaccine product within 4 weeks of study intervention administration (visit 2) or expected to receive a live or attenuated-live vaccine product during the treatment period. (Note: Not-live and not attenuated-live vaccines are not exclusionary.
34. Use of preventive systemic antibiotics, systemic antivirals, or systemic antifungals at screening (visit 1). (Note: “Systemic” is defined as oral or i.v. administered drugs that are absorbed into the circulation. Antibiotics used to treat latent TB are exempted).
35. Use of systemic immunosuppressive drugs (both small molecules and biologics) or disease modifying anti-rheumatic drugs (DMARDs including both biologic DMARDs like anti-TNF-alpha and conventional DMARDs like methotrexate) at screening (visit 1) or anticipated chronic use of such drugs any time during the study. (Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary).
36. Use of anti-IL-6 products at screening (visit 1) or anticipated use of such drugs any time during the study.