SBIR-STTR Award

The implementation of a modified Thrombelastograph Coagulation Analyzer (MTEG(TM)) with a new assay to monitor platelet glycoprotein Ilb/IIla (GPIIb/IIla) receptor blockade in patients being treated with the recently-approved antibody fragment c7E3 Fab is proposed. Based on preliminary results, we are confident that the study will show that the MTEG(TM) can provide an equivalent or better assessment of platelet GPIIb/IIla receptor blockade than the "gold standard" turbidometric platelet aggregation test (aggregation). Phase I research will focus on the study of platelet GPIIb/Illa blockade as measured by MTEG(TM) and aggregation on blood samples of patients undergoing PTCA adjunctive with c7E3 Fab treatment. Inhibition of platelet function, as measured by MTEG(TM), will be correlated with the aggregation response to ADP. Aggregation is a time-consuming test, is expensive to run and requires specially-trained personnel; therefore it is not readily available or practical for routine monitoring or dose individualization. MTEG(TM) can rapidly assay platelet function; it is inexpensive to run and easy to use; and can provide point-of-care monitoring of platelet GPIIb/IIla blockade. Phase II will validate the new test in a larger patient population undergoing PTCA. PROPOSED COMMERCIAL APPLICATIONS: Commercialize the MTEG and accompanying assay to provide a fast and easy- to-use point-of-care test of platelet GPIIb/IIIa blockade.

Thesaurus Terms:
biomedical equipment development, blocking antibody, clinical biomedical equipment, glycoprotein, immunotherapy, intraluminal angioplasty, method development, patient monitoring device, platelet aggregation clinical research, human subject

Phase I results show that the modified Thrombelastograph(R) Coagulation Analyzer (TEG(R)) assay to monitor platelet glycoprotein Ilb/IIIa (GPIIb/IIla) receptor blockade in patients being treated with c7E3 Fab provides an equivalent or better assessment of platelet GPIIb/IIla receptor blockade than the "gold standard" turbidimetric platelet aggregation test. Furthermore, in Phase I an individualized dosing algorithm with the use of the TEG(R) assay was developed. Using this algorithm, Phase II patients undergoing PTCA treated with c7E3 Fab can be individually dosed to achieve 80% reduction in Gp due to platelet inhibition. Further, Phase II will validate and expand the new test by: *Increasing the sample size to 400 to enhance the validity of the study, and increasing the participating hospitals to two, using institutions with a more diverse patient population. * Extending the Phase I study to encompass an additional GPIIb/IlIa inhibitor, eptibatide (Integrilin(TM)), to generalize the TEG(R) assessment of platelet GPIIb/IIla blockade. * Evaluating and refining the Phase I individualized dosing and comparing its clinical utility with the standard protocol of a weight-adjusted treatment of platelet blocker drugs to demonstrate reduced bleeding complications and decreased ischemic events and death. PROPOSED COMMERCIAL APPLICATIONS: The TEG(R) assay will be commercialized and used as a dedicated kit to monitor, assess and individualize dosing of GPIIb/IIia blockade in individuals being treated with c7E3 Fab, Integrilin or other new platelet inhibitor drugs.

Thesaurus Terms:
biomedical equipment development, blocking antibody, glycoprotein, immunotherapy, intraluminal angioplasty, patient monitoring device, platelet aggregation clinical biomedical equipment clinical research, human subject