Anticoagulation With rNAPc2 to Eliminate MACE/TIMI 32
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).
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind Placebo-Controlled Study to Assess the Safety of Factor VIIa/Tissue Factor Inhibitor, Recombinant Nematode Anticoagulant Protein c2 (rNAPc2), in Subjects With Non-ST-Elevation Acute Coronary Syndromes - ANTHEM (Anticoagulation With rNAPc2 to Help Eliminate MACE)/TIMI 32. Amendment #3 - A Single Arm, Open-Label Study of rNAPc2 With Reduced Doses of Unfractionated Heparin|
- Evaluation of the effects of a range of doses of rNAPc2 in subjects with non-STE acute coronary syndrome on safety and laboratory parameters from randomization until 7 days after the last dose of study drug
- Evaluation of the effects of a range of doses of rNAPc2 on the presence of ischemia following randomization as identified via continuous ST segment (Holter) monitoring
- Evaluation of the effects of a range of doses of rNAPc2 on pharmacodynamic and pharmacokinetic measures
- Evaluation of the effects of rNAPc2 on major cardiovascular clinical events over the period from randomization until six months following randomization
- Assessment of the ability of rNAPc2 to blunt the release of markers of necrosis
- Exploration of the relationship between genetic variation and rNAPc2 efficacy
- Evaluation of the efficacy and safety of rNAPc2 with reduced-dose (including no) unfractionated heparin (UFH)
|Study Start Date:||June 2005|
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.
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States|
|Study Director:||Steven Deitcher, MD||ARCA Biopharma, Inc.|