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

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

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

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: VIA-2291; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • Azienda Ospedali Riuniti Ancona
  • Avezzano, Italy
    • Presidio Ospedaliero SS Filippo e Nicola
  • Chieti Scalo, Italy
    • Centro Studi Sull'Invecchiamento

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tallikut Pharmaceuticals, Inc.
• Investigators: Study Director: Rebecca Taub, MD, VIA Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: July 12, 2006
• First Submitted That Met QC Criteria: July 12, 2006
• First Posted (Estimate): July 14, 2006

Study Record Updates

• Last Update Posted (Estimate): July 27, 2012
• Last Update Submitted That Met QC Criteria: July 19, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Inflammation; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipoxygenase Inhibitors; Atreleuton
• Other Study ID Numbers: VIA-2291-02; 2006-001635-21 (EudraCT Number)