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Dose-finding Study of YMI024 to Assess Efficacy, Safety, and Tolerability in Adults With Stable Coronary Artery Disease and Elevated hsCRP

14 octobre 2026 mis à jour par: Novartis Pharmaceuticals

A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Study of YMI024 to Assess Efficacy in Reducing Inflammatory Markers, Safety, and Tolerability in Adults With Stable Coronary Artery Disease and Elevated hsCRP

The purpose of this Phase 2b study is to investigate the efficacy in reducing systemic inflammation, safety, tolerability, and dose response of five doses of YMI024, as compared to placebo in adult participants with stable coronary artery disease (CAD) and residual inflammatory risk defined by elevated high-sensitivity C-reactive protein (hsCRP) (≥2 mg/L)

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

Participants are randomized in a 1:1:1:1:1:1 ratio to one of the six arms, with stratification by comorbidity status at randomization: CAD-only, CAD+ (Heart Failure) HF, and CAD+Chronic Kidney Disease (CKD), and receive study medication on top of stable standard-of-care therapies. The study employs double-blinding, concealing treatment allocation from participants, Investigators, Sponsor, and study staff, with identical packaging and labelling, schedule of administration and appearance for all study drugs.

Type d'étude

Interventionnel

Inscription (Estimé)

180

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

  • Nom: Novartis Pharmaceuticals
  • Numéro de téléphone: +41613241111

Lieux d'étude

  • Allemagne
      • Berlin, Allemagne, 10787
        • Recrutement
        • Novartis Investigative Site
      • Mannheim, Allemagne, 68165
        • Recrutement
        • Novartis Investigative Site
      • Pirna, Allemagne, 01796
        • Recrutement
        • Novartis Investigative Site
    • Baden-Wurttemberg
      • Stuttgart, Baden-Wurttemberg, Allemagne, 70376
        • Recrutement
        • Novartis Investigative Site
    • Rhineland-Palatinate
      • Kaiserslautern, Rhineland-Palatinate, Allemagne, 67655
        • Recrutement
        • Novartis Investigative Site
  • Australie
    • South Australia
      • Adelaide, South Australia, Australie, 5000
        • Recrutement
        • Novartis Investigative Site
    • Victoria
      • Frankston, Victoria, Australie, 3199
        • Recrutement
        • Novartis Investigative Site
      • Melbourne, Victoria, Australie, 8008
        • Recrutement
        • Novartis Investigative Site
      • Mulgrave, Victoria, Australie, 3170
        • Recrutement
        • Novartis Investigative Site
  • Japon
    • Aichi-ken
      • Kasugai, Aichi-ken, Japon, 4870016
        • Recrutement
        • Novartis Investigative Site
    • Chiba
      • Matsudo, Chiba, Japon, 2702251
        • Recrutement
        • Novartis Investigative Site
    • Kanagawa
      • Kamakura, Kanagawa, Japon, 2478533
        • Recrutement
        • Novartis Investigative Site
    • Osaka
      • Matsubara, Osaka, Japon, 5800032
        • Recrutement
        • Novartis Investigative Site
  • Royaume-Uni
      • London, Royaume-Uni, EC1A 7BE
        • Recrutement
        • Novartis Investigative Site
  • États-Unis
    • Alabama
      • Fairhope, Alabama, États-Unis, 36532
        • Recrutement
        • Eastern Shore Research Institute
        • Chercheur principal:
          • Michael S Pursley
        • Contact:
      • Foley, Alabama, États-Unis, 36535
        • Recrutement
        • G and L Research LLC
        • Chercheur principal:
          • Nidal Morrar
        • Contact:
    • California
      • Los Angeles, California, États-Unis, 90035
        • Recrutement
        • Biopharma Informatic LLC
        • Chercheur principal:
          • Christian Assad-Kottner
        • Contact:
    • Florida
      • Coral Gables, Florida, États-Unis, 33134
    • Kansas
      • Wichita, Kansas, États-Unis, 67207
        • Recrutement
        • Alliance for Multispecialty Research
        • Chercheur principal:
          • Saifullah Nasir
        • Contact:
    • Maryland
      • Ft. Washington, Maryland, États-Unis, 20744
      • Oxon Hill, Maryland, États-Unis, 20745
        • Recrutement
        • MD Medical Research
        • Chercheur principal:
          • Stephen T Ong
        • Contact:
    • Texas
      • Amarillo, Texas, États-Unis, 79106
        • Recrutement
        • Pharma Tex Research
        • Chercheur principal:
          • David Brabham
        • Contact:
    • Virginia
      • Winchester, Virginia, États-Unis, 22601
        • Recrutement
        • Selma Medical Associates
        • Contact:
        • Chercheur principal:
          • Philip O Donnell

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Signed informed consent must be obtained prior to any study specific procedures, and participant able to understand and comply with study requirements.

  2. Male and female participants aged between 18-80 years (inclusive) at Screening.

  3. Documented stable CAD as evidenced by presence of at least one of the following criteria:

    1. Documented history of spontaneous (Type 1) myocardial infarction (MI) of presumed atherosclerotic origin that occurred at least 30 days before the start of Screening. If a Pre-screening visit is conducted, the MI must have occurred at least 30 days before that visit.

      Diagnosis of the qualifying MI should be based on medical records and Investigator's judgment.

    2. Prior coronary revascularization (i.e. percutaneous coronary intervention (PCI) at least 30 days prior, or coronary artery bypass grafting (CABG), at least 6 months prior to Screening).

      • Any prior PCI must have occurred at least 30 days prior to the Screening Visit (or if conducted, prior to the Pre screening visit).
      • Any prior CABG must have occurred at least 6 months (i.e. 26 weeks) prior to the Screening (or if conducted, prior to the Pre-screening) Visit.

    3. Angiographic or CT-imaging (e.g., Multi Detector Computed Tomography/ Computed Tomography Angiography (MDCT/CTA)) evidence of coronary atherosclerosis: ≥50% stenosis in at least one major epicardial coronary artery.

    4. Coronary artery calcium (CAC) score of ≥300 AU by computed tomography.

    To ensure adequate representation of patients with clinically relevant comorbidities and to enable prespecified subgroup analyses, the trial will include participants with key comorbidities as follows:

    i. Moderate CKD Participants with moderate (Stage 3a/3b) kidney disease (CKD) defined as: Estimated Glomerular Filtration Rate (eGFR) ≥30 and ≤60 mL/min/1.73 m² (CKD EPI formula) at Screening.

    ii. Chronic HF

    Participants with a history of chronic heart failure (HF) defined as:

    • NYHA Class II-III symptoms of HF requiring ongoing treatment with diuretics (loop diuretics, thiazide diuretics, and/or mineralocorticoid receptor antagonists) for ≥30 days prior to Screening, AND
    • LVEF ≤40%, assessed by any standard modality (e.g., echocardiography, cardiac Magnetic Resonance Imaging (MRI), CT, MUGA, or ventricular angiography) on the most recent assessment within 12 months prior to Screening.

  4. Participants must have hsCRP levels ≥2 mg/L at two timepoints during Screening. Screening values must be separated by a minimum of 7 days. The initial hsCRP value must be a minimum of 30 days after a qualifying MI or after any PCI performed separately from the qualifying MI, or 6 months after CABG.

Note: Participants who choose to enter the optional Pre-screening period must have an hsCRP level, measured at a local laboratory, that is considered by the Investigator to be ≥2 mg/L. This Pre-screening hsCRP value (measured at the local laboratory) must be obtained at least 30 days after a qualifying MI or after any PCI performed separately from the qualifying MI, or 6 months after a CABG.

Irrespective of any Pre-screening hsCRP value, all participants must have two central laboratory hsCRP levels ≥2 mg/L at the two Screening visits to be eligible for randomization into the study.

Exclusion Criteria:

  1. Participants with recent major cardiovascular events or procedures, including:

    • myocardial infarction, unstable angina, or percutaneous coronary intervention within 30 days prior to Screening (or Pre-screening, if conducted), or
    • coronary artery bypass grafting or other cardiac surgery within 6 months prior to Screening (or Pre-screening, if conducted).

  2. Any major (cardiac or non-cardiac) surgical, interventional or endoscopic procedure (e.g: Percutaneous carotid intervention, carotid or peripheral arterial revascularization), or stroke, Transient ischemic attack (TIA), or acute limb ischemia within 12 weeks prior to Screening or Pre-screening, where applicable).

  3. Participants with a known systemic autoimmune or inflammatory disease (e.g., Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA)); clinically active diverticulitis or inflammatory bowel disease within 12 months prior to Screening; or a history of gastrointestinal perforation.

  4. Patients with suspected or proven immunocompromised state at Screening (e.g., clinical diagnosis of Human Immunodeficiency Virus (HIV) or on antiretroviral therapy, absolute neutrophil count ≤1000/mm3) or any other medical condition in the opinion of the Investigator places the patient at unacceptable risk by receiving immunomodulatory therapy.

  5. Known or suspected active infection, or chronic or recurrent infectious disease, including but not limited to:

    • Hepatitis B / Hepatitis C: Positive HBsAg, positive anti-HBc, positive anti-HBs, or positive anti-Hepatitis C Virus (HCV) at Screening.
    • Note: Participants positive for anti-HBs after HBV vaccination but negative for HBsAg and anti-HBc are eligible per local guidelines and Sponsor agreement.
    • Note: Participants positive for anti-HBc but negative for HBV Deoxyribonucleic Acid (DNA) receiving prophylactic HBV antiviral treatment (e.g., entecavir, lamivudine) are eligible per local guidelines and Sponsor agreement.
    • Note: Participants positive for anti-HCV but consistently negative for HCV RNA >6 months after HCV antiviral treatment are eligible per local guidelines and Sponsor agreement.
    • Tuberculosis (TB): Active or latent TB as indicated by a positive QuantiFERON® TB Gold Plus test or T-SPOT® TB test at Screening.
    • Any other known active or suspected active infection, or chronic infection, or history of ongoing, chronic, or major recurrent infectious disease.

  6. Participants with any of the following renal or hepatic abnormalities at Screening are excluded:

    1. Renal dysfunction with Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m² (using CKD-EPI formula; s://.kidney.org/professionals/gfr_calculator).
    2. Evidence of hepatic disease as determined by any one of the following: Aspartate Aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) or Alanine Aminotransferase (ALT) (Serum Glutamic Pyruvic Transaminase (SGPT)) >3× ULN, or bilirubin >1.5 mg/dL at Screening (for patients with Gilbert's syndrome, total bilirubin <2× ULN is allowed).

  7. Current or prior history of severe heart failure of New York Heart Association (NYHA) Class IV.

Other protocol-defined inclusion/exclusion criteria may apply

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: YMI024 Dose 1

Participants receive YMI024 Dose 1 in addition to standard-of-care therapies.
Médicament: YMI024

YMI024 in different doses
Expérimental: YMI024 Dose 2

Participants receive YMI024 Dose 2 in addition to standard-of-care therapies.
Médicament: YMI024

YMI024 in different doses
Expérimental: YMI024 Dose 3

Participants receive YMI024 Dose 3 in addition to standard-of-care therapies.
Médicament: YMI024

YMI024 in different doses
Expérimental: YMI024 Dose 4

Participants receive YMI024 Dose 4 in addition to standard-of-care therapies.
Médicament: YMI024

YMI024 in different doses
Expérimental: YMI024 Dose 5

Participants receive YMI024 Dose 5 in addition to standard-of-care therapies.
Médicament: YMI024

YMI024 in different doses
Comparateur placebo: Placebo

Participants receive a matching placebo in addition to standard-of-care therapies
Médicament: Placebo

matching placebo

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Change from baseline in log-transformed IL-6
Délai: Baseline and approximately 3 months

Change from baseline in log-transformed Interleukin-6 (IL-6) to evaluate the dose-response relationship using the Multiple Comparison Procedures (MCP) component of the Multiple Comparison Procedure-Modelling (MCP-Mod) methodology
Baseline and approximately 3 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change from baseline in log-transformed IL-6
Délai: Baseline and approximately 3 months

Change from baseline in log-transformed IL-6 to characterize the dose-response relationship for YMI024 in IL-6 using the model-based (Mod) component of the MCP-Mod methodology
Baseline and approximately 3 months
Change from baseline in log-transformed hsCRP
Délai: Baseline and approximately 3 months

Change from baseline in log-transformed high-sensitivity C-reactive protein (hsCRP)
Baseline and approximately 3 months
Responder status - hsCRP <2 mg/L
Délai: Approximately 3 months

Responder status (Yes/No), defined as hsCRP <2 mg/L
Approximately 3 months
Responder status - hsCRP <1 mg/L
Délai: Approximately 3 months

Responder status (Yes/No), defined as hsCRP <1 mg/L
Approximately 3 months
Number of participants with adverse events
Délai: Approximately 4 months

Number of participants with adverse events, including abnormal vital signs, ECGs, and laboratory assessments
Approximately 4 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Pharmaceuticals

Les enquêteurs

  • Directeur d'études: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

18 septembre 2026

Achèvement primaire (Estimé)

15 août 2027

Achèvement de l'étude (Estimé)

15 août 2027

Dates d'inscription aux études

Première soumission

15 septembre 2026

Première soumission répondant aux critères de contrôle qualité

15 septembre 2026

Première publication (Réel)

21 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

15 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

14 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CYMI024A12202
  • U1111-1339-3893 (Autre identifiant: UTN number)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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