Atherosclerosis
Conditions
Brief summary
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
Interventions
DRUGVIA-2291
100 mg, oral dosing, 1 time daily for 12 weeks
DRUGPlacebo
oral dosing, 1 time daily for 12 weeks
Sponsors
Tallikut Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Cross-sectional Area of Macrophages in Plaque Tissue | 12 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | Baseline and 12 weeks | — |
| Percent Cross-sectional Area of Anti-5-Lipoxygenase Staining in Plaque Tissue | 12 weeks | 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 |
| 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 | — |
Countries
Italy
Participant flow
Recruitment details
Patients recruited from three Italian Medical Centers
Participants by arm
| Arm | Count |
|---|---|
| VIA-2291 100-mg dose | 24 |
| Matching Placebo Placebo Dose | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Schedule Change | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Matching Placebo | VIA-2291 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 13 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 11 Participants | 19 Participants |
| Age Continuous | 69.5 years STANDARD_DEVIATION 8.73 | 66.8 years STANDARD_DEVIATION 8.86 | 68.2 years STANDARD_DEVIATION 8.81 |
| Region of Enrollment Italy | 26 participants | 24 participants | 50 participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 24 | 9 / 26 |
| serious Total, serious adverse events | 4 / 24 | 1 / 26 |
Outcome results
Primary
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
Time frame: 12 weeks
Population: Evaluable Population with histological sections available
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VIA-2291 | Percent Cross-sectional Area of Macrophages in Plaque Tissue | 8.08 Percent Area |
| Matching Placebo | Percent Cross-sectional Area of Macrophages in Plaque Tissue | 8.19 Percent Area |
p-value: 0.97t-test, 2 sided
Secondary
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP)
Time frame: Baseline and 12 weeks
Population: Evaluable population with both baseline and visit 8 results
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| VIA-2291 | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | -2.0 mg/L |
| Matching Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | 0.2 mg/L |
p-value: <0.01ANCOVA
Secondary
Change From Baseline in Urine Leukotriene E4 Adjusted for Creatinine
Time frame: Baseline and 12 Weeks
Population: Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VIA-2291 | Change From Baseline in Urine Leukotriene E4 Adjusted for Creatinine | -64.7 Percent Change |
| Matching Placebo | Change From Baseline in Urine Leukotriene E4 Adjusted for Creatinine | -15.5 Percent Change |
p-value: <0.01ANCOVA
Secondary
Change From Baseline in Whole Blood Leukotriene B4 Production
Time frame: Baseline and 12 weeks
Population: Evaluable Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| VIA-2291 | Change From Baseline in Whole Blood Leukotriene B4 Production | -123,000 pg/ml |
| Matching Placebo | Change From Baseline in Whole Blood Leukotriene B4 Production | -42,900 pg/ml |
p-value: <0.0001ANCOVA
Secondary
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
Time frame: 12 weeks
Population: Evaluable Population with histological sections available
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VIA-2291 | Percent Cross-sectional Area of Anti-5-Lipoxygenase Staining in Plaque Tissue | 1.80 Percent Area |
| Matching Placebo | Percent Cross-sectional Area of Anti-5-Lipoxygenase Staining in Plaque Tissue | 0.87 Percent Area |
p-value: 0.37t-test, 2 sided