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

Korábbi kezelés

• 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).
• 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).
• 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.
• 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.
• Current or prior history of severe heart failure of New York Heart Association (NYHA) Class IV.
  • Other protocol-defined inclusion/exclusion criteria may apply

Laborértékek

• 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.
• Participants with any of the following renal or hepatic abnormalities at Screening are excluded:
  • Renal dysfunction with Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m² (using CKD-EPI formula; s://.kidney.org/professionals/gfr_calculator).
  • 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).

• Signed informed consent must be obtained prior to any study specific procedures, and participant able to understand and comply with study requirements.
• Male and female participants aged between 18-80 years (inclusive) at Screening.
• Documented stable CAD as evidenced by presence of at least one of the following criteria:
  • 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.
  • 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.
  • 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.
  • 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:
  • 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.
  • 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.
• 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.