Study Effect of VIA-2291 on Atherosclerotic Vascular Inflammation in Patients Undergoing Elective Carotid Endarterectomy

Study Overview
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Brief Summary
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This is a study to compare the effect of VIA-2291 vs. Placebo on various inflammatory biomarkers in patients with carotid stenosis scheduled for elective carotid endarterectomy

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled Study of the Effects of VIA-2291, a 5-Lipoxygenase Inhibitor, on Atherosclerotic Plaque and Biomarkers of Vascular Inflammation in Patients With Carotid Stenosis Undergoing Elective Carotid Endarterectomy

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: VIA-2291
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients must be of non-childbearing potential Carotid stenosis between 60% and 90% and to be scheduled for CEA surgery One or more of the following clinical features: Prior history >4 weeks of cerebrovascular accident (CVA) or transient ischemic attack (TIA) consistent with North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria or prior history of amaurosis fugax occurring at any time Diabetes haemoglobin (Hb) A1c between 7.0 and 11% or a history of two or more fasting blood glucose levels >6.9 mmol/L Baseline hsCRP >2 mg/L Echolucent plaque Exclusion Criteria: Acute CVA or TIA within 4 weeks of enrollment or the presence of ulcerated or unstable plaque requiring urgent carotid endarterectomy Renal insufficiency defined as creatinine >1.5 x upper limit of normal (ULN) Cirrhosis, recent hepatitis, alanine aminotransferase (ALT) >1 x ULN (i.e., above the normal range) or positive screening test for hepatitis B (hepatitis B surface antigen) or hepatitis C (by ELISA) Uncontrolled diabetes mellitus within 1 month prior to study screening, defined as HbA1c >11% at screening Congestive heart failure (CHF) defined by the New York Heart Association as functional Class III or IV Recent acute coronary syndrome event or coronary artery bypass graft (CABG) surgery (within 4 weeks of enrollment) Current atrial fibrillation Planned cardiac intervention Acetaminophen use in any form in the 7 days before enrollment

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIA-2291<br> | Drug: VIA-2291<br>* 100 mg, oral dosing, 1 time daily for 12 weeks<br>* Other names: atreleuton;|
| Placebo Comparator: Placebo<br>Matching Placebo | Drug: Placebo<br>* oral dosing, 1 time daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Cross-sectional Area of Macrophages in Plaque Tissue | Effect of VIA-2291 100-mg relative to placebo after 12 weeks of daily dosing on the percent cross-sectional area of macrophages in plaque tissue using an anti-CD68 antibody | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Cross-sectional Area of Anti-5-Lipoxygenase Staining in Plaque Tissue | Effect of VIA-2291 100-mg relative to placebo after 12 weeks of daily dosing on the percent cross-sectional area of anti-5-Lipoxygenase staining in plaque tissue | 12 weeks | 
| Change From Baseline in Whole Blood Leukotriene B4 Production |  | Baseline and 12 weeks | 
| Change From Baseline in Urine Leukotriene E4 Adjusted for Creatinine |  | Baseline and 12 Weeks | 
| Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) |  | Baseline and 12 weeks |