Safety and Preliminary Efficacy Study of an Anti-inflammatory Therapeutic Antibody in Reducing Restenosis.

Study Overview
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Brief Summary
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The purpose of this study is to determine if CV-18C3 will reduce the rate of restenosis or the time to restenosis in patients undergoing repeat peripheral artery revascularization versus controls randomized to standard of care.

Detailed Description
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Restenosis of peripheral artery lesions remains a challenging problem to overcome after percutaneous revascularization of atherosclerotic disease in the femoropopliteal arterial system. Rates of restenosis are as high as 60% after a year. Treatment options include medical therapy, angioplasty, arthrectomy and stent placement. The heterogeneity of disease between patients, variable length of target lesions and presence of unpredictable physical forces requires individualized treatment plans. Vascular response to injury appears to play an important role in the development of restenosis. IL-1α is a potent inflammatory cytokine that plays a central role in vascular inflammation and vascular smooth muscle proliferation--both in acute and chronic injury. CV-18C3 antagonizes the biologic activity of IL-1α and is theorized to prevent the early IL-1α mediated inflammation that leads to vascular smooth muscle hypertrophy and restenosis, as well as the late IL-1α mediated atherosclerotic plaque formation.

Official Title
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Phase II Open Label,Randomized Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of an Anti-Inflammatory Therapeutic Antibody(CV-18C3)in Reducing Restenosis in Patients Undergoing Percutaneous Femoro-popliteal Revascularization.

Conditions
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Patients Undergoing Repeat Peripheral Artery Revascularization

Intervention / Treatment
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* Drug: CV-18C3
* Procedure: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have suspected superficial femoro-popliteal artery occlusion due to lower extremity pain with exercise or at rest and are undergoing a planned arteriogram. Subjects will be randomized after angiographic evidence of qualifying lesion Exclusion Criteria: Acute critical limb ischemia History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CV-18C3 and standard of care<br>CV-18C3 and standard of care | Drug: CV-18C3<br>* 3.75mg/kg given IV for a period of 6 weeks, followed by subcutaneous administration<br>Procedure: Standard of Care<br> <br> |
| Active Comparator: standard of care<br>Percutaneous revascularization | Procedure: Standard of Care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of CV-18C3 | adverse events, vitals signs, physical examination results and clinical laboratory values | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to restenosis and restenosis rates compared between CV-18C3 and controls | Efficacy determination will be derived from observed rates of target vessel occlusion, time to occlusion, incidence of target vessel revascularization procedures and incidence of major adverse cardiovascular events (MACE). ABI measurements and quality of life questionnaire scores will also be collected. Treated subjects will be compared to those randomized to no treatment. | 1 year |