Safety, Tolerability and Efficacy of ACZ885 on Leg Artery Structure in Patients With Peripheral Artery Disease

Study Overview
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Brief Summary
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This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg artery structure and physical activity in patients with atherosclerotic peripheral artery disease and leg pain from walking.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Effects on Arterial Structure and Function of ACZ885 in Patients With Intermittent Claudication.

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Drug: Canakinumab (ACZ885)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a signed informed consent form. Must be between the ages of 18 and 85 Must experience leg pain associated with walking and have an ankle brachial index between 0.40 and 0.9 Must be on stable aspirin and statin doses for at least 6 weeks Blood pressure within ranges specified in the protocol Able to communicate well with the Investigator and understand and comply with the study procedures Key Exclusion Criteria: Recent use of any other experimental drugs Pregnant or nursing women Women of child bearing potential unless willing to use contraception as detailed in the protocol Cannot walk 15 meters (50 feet) People on restricted medications as listed in the protocol Any open or non-healing wounds with 3 months of study start or infection within 2 weeks or study start Significant heart disease Uncontrolled diabetes Significant kidney or liver disease Live vaccinations within 3 months of study start History of untreated tuberculosis or active tuberculosis (TB) Patients with metal in their body (excluded due to MRI scan) as detailed in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab (ACZ885)<br>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months | Drug: Canakinumab (ACZ885)<br>* Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.<br>|
| Placebo Comparator: Placebo<br>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months | Drug: Placebo<br>* Matching placebo of Canakinumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Vessel Wall Area Ratio of 12 Months to Baseline | Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. | Baseline, 12 months post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events in 12 Months | Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death. | Baseline to 12 months post-dose | 
| Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline | Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. | Baseline, 12 months post-dose | 
| High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline | Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. | Baseline, 12 months post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral artery disease, Intermittent claudication, magnetic resonance imaging