Anticoagulation With rNAPc2 to Eliminate MACE/TIMI 32
Condition: Coronary Disease
MeSH terms: Acute Coronary Syndrome; Coronary Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary focus of this study is to explore the safety of a range of doses of rNAPc2 in
      subjects who are managed in hospitals that most typically practice an early invasive strategy
      (catheterization during the index admission). After completion of the ascending dose-ranging
      part of the trial and review of these data by the Data and Safety Monitoring Board (DSMB),
      the maximum tolerated dose of rNAPc2 will be studied in single-arm, open-label panels
      (approximately 25 subjects each) of rNAPc2 with descending doses of unfractionated heparin
      (UFH).
    

Detailed description: 
      Acute coronary syndromes (ACS), which include unstable angina and non-ST-elevation (non-STE)
      myocardial infarction, represent a serious clinical condition affecting over 1,000,000 people
      in the US alone. The combined rate of death and myocardial infarction (MI) in ACS patients is
      8-15% after one month, in spite of the best current therapy including use of low-molecular
      weight heparins, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and an early invasive
      strategy. Given the high prevalence of the disorder, further improvements in the outcomes in
      these patients are very desirable.

      It is currently believed that the principle cause of the clinical symptoms characterizing ACS
      results from the transient thrombotic occlusion of one or more coronary vessels. Coronary
      thrombosis is initiated by the exposure of the protein tissue factor (TF), which can be found
      in the sub-endothelial layer of the blood vessel and is a major component of atherosclerotic
      gruel. The exposure of TF following vascular damage or rupture of a coronary atherosclerotic
      plaque, results in the rapid formation of the enzymatic complex composed of TF and the serine
      protease factor VIIa (fVIIa/TF). The fVIIa/TF complex initiates an amplified cascade of
      proteolytic activation steps resulting in the formation of the serine protease thrombin. The
      highly amplified generation of thrombin localized to the site of vascular damage or plaque
      rupture, coupled with the high-shear rheological environment of the coronary vessel, results
      in the activation and subsequent aggregation of platelets and the formation of an insoluble
      matrix of fibrin resulting in a platelet-rich thrombus.

      The critical role of the fVIIa/TF complex in the initiation of coronary thrombosis suggests
      that it may be an ideal target for inhibitors that will result in an attenuation of thrombin
      generation and subsequent thrombus formation. Recombinant nematode anticoagulant protein c2
      (rNAPc2) is a novel and potent inhibitor of fVIIa/TF that may improve current therapeutic
      strategies in reducing the extent of coronary thrombosis and subsequent clinical events in
      patients diagnosed with ACS.
    

Intervention name(s): rNAPc2
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: acute coronary syndrome; rNAPc2; unstable angina; Non-STE myocardial infarction; ST elevation; cardiac enzymes; acute coronary syndromes; factor VIIa; tissue factor; nematode anticoagulant protein c2; anticoagulants; thrombin inhibitors; thrombosis