Study of Alfimeprase's Ability to Dissolve Blood Clots in the Leg and Help Prevent the Need for Surgery

Phase 3, Multicenter, Multi-National, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alfimeprase in Subjects With Acute Peripheral Arterial Occlusion (NAPA-3)

The purpose of this study is to directly compare the safety and efficacy of intra-thrombus alfimeprase 0.3 mg/kg with placebo in acute peripheral arterial occlusion (PAO) as measured by a 30 day open vascular free surgery rate.

There is an unmet medical need to improve thrombolytic therapy in acute peripheral arterial occlusion (PAO). Currently used plasminogen activators can result in increased circulating levels of plasmin that result in a systemic "lytic state" that does not distinguish between physiologic and pathologic thrombosis. In general, mean plasminogen activator infusion durations of greater than 24 hours in order to achieve successful thrombolysis are problematic in a disease where delayed restoration of arterial flow can lead to irreversible ischemic damage. A direct thrombolytic agent like alfimeprase, with a rapid mechanism of action and a potentially safer bleeding risk profile, could facilitate a rapid restoration of arterial flow and avoidance of open vascular surgery.

Inclusion Criteria:

• Age 18 or older
• Arteriographically confirmed acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization
• Acute index limb ischemia classified as SVS/ISCVS Class I or IIa caused by occlusion of a native artery and/or bypass graft (vein or prosthetic). Only Class I subjects with abrupt onset of ischemic rest pain or abrupt onset/progression of lifestyle-limiting claudication are eligible
• Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy
• Available for follow-up assessments

Exclusion Criteria:

• Contraindication to systemic anticoagulation
• History of endovascular procedure or open vascular surgery on the index limb within the past 30 days
• History of significant acute or chronic kidney disease that would preclude contrast angiography
• Known allergy to contrast agents
• History of heparin induced thrombocytopenia
• Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization
• Any thrombolytic therapy within 5 days prior to randomization
• Past participation in any alfimeprase trial
• Pregnant, lactating, or actively menstruating women or women of childbearing potential who are not using adequate contraceptive precautions
• Investigator inability to advance guidewire through index occlusion
• Any other subject feature that in the opinion of the investigator should preclude study participation