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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2015

Interventions

  • Biological: Plasmin
    • Plasmin prepared in 0.9% saline for injection
  • Biological: Plasminogen Activator
    • Plasminogen activator used according to the Investigator’s clinical judgment.
  • Other: Placebo
    • Normal saline for injection at the same volume as the plasminogen activator.

Arms, Groups and Cohorts

  • Experimental: Plasmin Open-label Treatment Group A
    • Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.
  • Experimental: Plasmin Open-label Treatment Group B
    • Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate
  • Experimental: Plasmin Open-label Treatment Group C
    • Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
  • Experimental: Plasmin Open-label Treatment Group D
    • Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
  • Active Comparator: Plasminogen Activator Blinded Group E
    • PA administered for five hours at a dose and volume according to the Investigator’s clinical judgement/standard practice
  • Placebo Comparator: PA Placebo Blinded Treatment Arm F
    • PA placebo (normal saline for injection) administered for five hours at a dose and volume according to the Investigator’s clinical judgement/standard practice for PA administration
  • Experimental: Plasmin Open-label Treatment Group G
    • Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
  • Experimental: Plasmin Open-label Treatment Group H
    • Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
  • Experimental: Plasmin Open-label Treatment Group I
    • Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
  • Experimental: Plasmin Open-label Treatment Group J
    • Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter
  • Experimental: Plasmin Open-label Treatment Group M
    • Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter

Clinical Trial Outcome Measures

Primary Measures

  • The Proportion of Subjects With >50% Thrombolysis
    • Time Frame: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
    • The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography.

Secondary Measures

  • The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.
    • Time Frame: 30 days
    • The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Grifols Therapeutics LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Kecia Courtney, Study Director, Grifols Therapeutics

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