A Study of Intra-thrombus Plasmin (Human) In Acute Peripheral Arterial Occlusion

A Phase 2, Randomized, Open-label (With Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusion

The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.

Inclusion Criteria:

• Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa
• Onset of symptoms less than or equal to 14 days
• Thrombosed infrainguinal bypass graft or native artery
• Diagnosis by arteriography of occlusive thrombus in graft or artery
• Ability to embed the infusion catheter into the thrombus
• Women of childbearing potential must use contraception and have a negative pregnancy test

Exclusion Criteria:

• Any medical or social condition that may interfere with study participation
• Women who are pregnant or lactating
• Hemorrhagic stroke history
• Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year
• Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months
• Major surgery, organ biopsy, or major trauma within the past 10 days
• Lumbar puncture or non-compressible arterial puncture in the past 10 days
• Intraocular surgery within the past 10 days
• Active gastrointestinal or organ bleeding
• Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
• Known intracranial neoplasm, aneurysm, or arteriovenous malformation
• Current bleeding diathesis
• Platelet count <75 x 10e9/L
• Active graft infection
• Occlusion occurred within one month of synthetic graft placement
• Occlusion occurred within 6 months of autologous graft placement
• A sequential composite graft with dual outflows to correct multiple occlusions
• Medically unable to tolerate an open vascular procedure
• Known prothrombotic state
• Hemoglobin <10.0 g/dL
• Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine >2.0 mg/dL
• Treatment with a full dose plasminogen activator (PA) within the last 48 hours
• Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days
• Treatment with oral anticoagulants, and with an international normalized ratio of >1.7