Patients with stable coronary artery disease and high cardiovascular risk MedDRA version: 20.0 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: IZD334
Product Code: IZD334
Pharmaceutical Form: Capsule
INN or Proposed INN: selective NLRP3 inhibitor
CAS Number: 2260969-36-4
Current Sponsor code: IZD334
Other descriptive name: IZD3
Sponsors
Inflazome Ireland Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent form obtained before any study assessment is performed 2. Male or female patients aged =18 years 3. Stable coronary artery disease (CAD) where stable coronary artery disease refers to any of the following: a. a reversible supply/demand mismatch related to ischemia or b. a history of myocardial infarction (minimum 30 days prior to randomization) or c. the presence of coronary artery plaque of any severity documented by cardiac catheterization or computed tomography angiography. Patients are considered stable if they are asymptomatic or their symptoms are adequately controlled by medications or revascularization. 4. Elevated plasma CRP level of = 2 mg/L at screening visit 1 (local lab) and confirmed at screening visit 2 by central lab 5. Negative pregnancy test for females of child-bearing potential (premenopausal, ? 2 years post-menopausal, not surgically sterile) 6. Stable concomitant medication for at least 4 weeks prior to randomization 7. Patients with creatinine clearance ? 30 mL/min/1.73m2 by the MDRD (modification of diet in renal disease) equation may be included Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 92 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Any use of NSAIDs or steroids or cholchicine or anti-IL-1 inhibitors within 4 weeks prior to randomization (ASS 100mg as part of SOC treatment is allowed / topical, inhaled, local steroid use in doses that are not considered to cause systemic effects are permitted) 2. Any investigational drugs or participation in a clinical trial within 4 weeks or five half-lives (whichever is longer) prior to randomization 3. Active systemic infections (other than common cold) during the two weeks prior to randomization 4. Positive test for hepatitis B virus surface antigen (HBsAg) or Hepatitis C virus RNA at screening 5. Positive test for HIV at screening 6. History of severe hypersensitivity according to the investigator’s judgement to previous drugs of similar chemical classes 7. Any severe, progressive or uncontrolled medical condition at baseline that in the judgment of the investigator prevents the patient from participating in the study including uncontrolled hypertension, uncontrolled diabetes and severe hepatic disease 8. Symptomatic patients with Class IV heart failure (HF) (New York Heart Association) 9. Planned Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Grafting (CABG) 10. Any clinically significant abnormal laboratory tests at screening 11. A history of alcohol and/or substance abuse that could interfere with the conduct of the trial 12. Inability or unwillingness to undergo repeated venipunctures (e.g., due to poor tolerability or lack of access to veins) 13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (HCG) laboratory test (> 5 mIU/mL) 14. Women of childbearing potential unwilling or unable to practice effective method of contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Investigate the safety and tolerability of oral IZD334 in patients with high cardiovascular risk • Evaluate the percent change from baseline of 450mg IZD334 compared to placebo in plasma C-reactive protein (CRP) after 12 weeks of treatment ;Secondary Objective: • Evaluate the percent change from baseline of 150mg IZD334 compared to placebo in plasma CRP after 12 weeks of treatment • Evaluate the percent change from baseline of 50mg IZD334 compared to placebo in plasma CRP after 12 weeks of treatment • Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 450mg IZD334 compared to placebo after 12 weeks of treatment • Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 150mg IZD334 compared to placebo after 12 weeks of treatment • Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 50mg IZD334 compared to placebo after 12 weeks of treatment;Primary end point(s): Mean change in CRP at 12 weeks of 450mg IZD334 compared to placebo ;Timepoint(s) of evaluation of this end point: At Week 12 (End of treatment visit) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Measurement of reduction of CRP in % from baseline to week 12 of 150mg IZD334 treatment • Measurement of reduction of CRP in % from baseline to week 12 of 50mg IZD334 treatment • Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 450mg IZD334 treatment • Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 150mg IZD334 treatment • Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 50mg IZD334 treatment • Determination of other inflammatory biomarkers at week 12 compared to baseline as markers for elevated risk for MACE. The following biomarkers are investigated: IL-6, IL-18, caspase-1, IL-1b, ASC and TNFa;Timepoint(s) of evaluation of this end point: At Week 12 (End of treatment visit) | — |
Countries
Netherlands
Contacts
Public ContactDirector Clinical Operations
Inflazome UK Ltd.
Outcome results
None listed