Safety/Feasibility of Vonapanitase Following Angioplasty for Patients With Peripheral Artery Disease (PAD) Below the Knee (BTK)

Screening: Initial study inclusion criteria

• Age of at least 18 years.
• Clinical diagnosis of PAD secondary to atherosclerosis affecting a lower limb.
• Rutherford category 3-5.
• De novo lesion, not previously treated by angioplasty, atherectomy or stenting.
• Scheduled to undergo angioplasty of the distal popliteal, tibial or peroneal arteries.
• If female and of childbearing potential (premenopausal and not surgically sterile) must have a negative pregnancy test at the screening visit and be willing to use contraception from the time of the screening visit to 1 week following study drug administration. Acceptable methods of birth control include abstinence, barrier methods with spermicide, implants, injectables, oral contraceptives, intra-uterine device, or a vasectomized partner.
• Ability to understand and comply with the requirements of the entire study and communicate with the study team.
• Ability to provide written informed consent using a document that has been approved by the required institutional review board.

Procedure: Study inclusion criteria to be determined at the time of the angioplasty procedure

• Atherosclerotic lesion with >50% stenosis in the popliteal (distal to the center of the knee joint space, the P3 segment), tibial or peroneal artery prior to angioplasty.
• Successful revascularization without the use of stenting of the target lesion; no flow limiting dissection and <30% residual lumen stenosis as compared with an adjacent non-diseased lumen diameter.

Exclusion criteria

Screening: Initial study exclusion criteria

• Patients in whom arterial insufficiency in the lower extremity is the result of an immunologic or inflammatory non-atherosclerotic disorder (e.g., Buerger's disease, vasculitis).
• Planned above ankle amputation on ipsilateral limb within 4 weeks of study drug administration.
• Prior or planned stenting of the target lesion.
• Deep vein thrombosis within the past 3 months.
• Known bleeding disorder.
• Known hypercoagulable state (e.g., protein C deficiency, factor V Leiden, prothrombin G20210A mutation).
• Platelet count <130K, hematocrit <30%, bilirubin or ALT >3.0 times the upper limit of normal.
• Renal failure with existing dependence on dialysis or an eGFR by MDRD calculation of < 20 mL/min/1.73 m2.
• Pregnancy, lactation or plans to become pregnant during the course of the study.
• Presence of any significant medical condition that might significantly confound the collection of safety and efficacy data in this study.
• Malignancy or treatment for malignancy within the previous 12 months with the exception of localized basal cell or squamous cell skin cancer, or any cancer in situ.
• Treatment with any investigational drug within the previous 30 days or investigational antibody therapy within 90 days prior to signing informed consent.
• Known allergy to radiocontrast agents.

Procedure:

Exclusion criteria

to be determined at the time of the angioplasty procedure

• Reference vessel diameter < 2 mm and > 8 mm.
• Severe concentric medial calcification of the target lesion thought to interfere with study drug delivery to the adventitia based on fluoroscopic appearance.
• Aneurysm in the target vessel.
• Failure to cross the target lesion with a guide wire; however subintimal wire crossing is allowed.
• Stenting of the target lesion.