A Study of Clazakizumab (LY5724886) in Adults With Elevated hsCRP and at Increased Risk for Cardiovascular Event

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Clazakizumab in Reducing hsCRP in Adults With Elevated hsCRP and Established ASCVD or at Increased Risk for ASCVD Events

The purpose of this study is to measure the change in high-sensitivity C-reactive protein (hsCRP), a marker of inflammation in the body, with clazakizumab compared with placebo in adults who have elevated hsCRP and at increased risk for cardiovascular event.

Participation in the study will last about 9 months.

Inclusion Criteria:

• hsCRP ≥2 mg/L and ≤15 mg/L at screening

• At least one of the following chronic conditions:

  • Established atherosclerotic cardiovascular disease (ASCVD)
  • Obesity (body mass index (BMI) ≥30 kg/m2)
  • Type 2 diabetes
  • Hypertension
  • Chronic kidney disease Grade 3 or 4

Exclusion Criteria:

• Acute cardiovascular event within 60 days prior to screening
• Acute decompensated heart failure hospitalization within 60 days prior to screening
• Planned coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or major surgery at the time of randomization
• New York Heart Association Class III or IV heart failure
• Uncontrolled hypertension at screening (systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg)
• Type 1 diabetes
• Type 2 diabetes with Hemoglobin A1c ≥9.0% (86 mmol/mol) at screening
• Nephrotic syndrome, estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m², or history of kidney transplant
• Dialysis or acute kidney injury within 60 days prior to screening
• Congenital/hereditary kidney disease, polycystic kidney disease, lupus nephritis, or antineutrophil cytoplasmic antibody-associated vasculitis
• Active tuberculosis, untreated latent tuberculosis, or known hepatitis B or hepatitis C infection
• Serious, opportunistic, chronic, or recurrent infection requiring treatment within 12 weeks prior to screening
• Significant active autoimmune disease
• Suspected or confirmed immunocompromised state (e.g., HIV infection)
• History of peptic ulcer disease or gastrointestinal ulceration within 12 months prior to screening
• History of diverticular disease, gastrointestinal perforation, or major gastrointestinal surgery
• Mechanical heart valve prosthesis requiring chronic vitamin K antagonist anticoagulation
• Use of colchicine within 14 days prior to screening or anticipated need during the study
• Use of immunosuppressive or immunomodulatory agents, including other biologic anti-IL-6 therapies, within specified windows prior to screening
• Use of systemic corticosteroids within 14 days prior to screening
• Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs)