Improved Factor VIII Inhibitor Evaluation
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Anemia, Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/21/2016 |
| Start Date: | July 2016 |
| End Date: | December 2017 |
Commercial one and two-stage factor VIII assays may not detect some clinically significant
inhibitor antibodies. The purpose of the proposed study is to standardize and validate a
platelet-based factor VIII activity assay with greater sensitivity to clinically important
inhibitory antibodies. Investigators will evaluate the platelet-dependent inhibitory
activity vs. conventional inhibitory activity in stored patient plasmas and correlate to
bleeding histories
inhibitor antibodies. The purpose of the proposed study is to standardize and validate a
platelet-based factor VIII activity assay with greater sensitivity to clinically important
inhibitory antibodies. Investigators will evaluate the platelet-dependent inhibitory
activity vs. conventional inhibitory activity in stored patient plasmas and correlate to
bleeding histories
Factor VIII activity assays are used to diagnose hemophilia A, to monitor treatment of these
patients, to determine when inhibitory antibodies against factor VIII have developed, and to
evaluate the activity of engineered pharmaceutical factor VIII products. Factor VIII
activity has been measured with one and two-stage assays for more than fifty years. However,
all existing assays have major shortcomings that are recognized by the FDA, the
International Society for Thrombosis and Haemostasis, and pharmaceutical companies. The
major deficiencies that have been identified are: 1) Factor VIII activity levels do not
predict the risk of bleeding in patients with inhibitory antibodies. The degree of
inhibition in these assays is less than required to explain patient bleeding. 2) The assays
are only accurate over a range of 1 - 100% of normal factor VIII activity, while values of
0.1 - 1% are also clinically important. 3) The different approved assays give discrepant
values for recombinant pharmaceutical factor VIII products, with a range of 2-fold
difference between assays. This can lead to clinically important differences in dosing of
factor VIII products from one region to another with corresponding risk of thrombosis or
bleeding.
The preliminary data identify an additional deficiency of commercial assays that has not
been anticipated. Commercial one and two-stage assays may not detect some clinically
significant inhibitor antibodies. Thus, the purpose of the proposed studies is to
standardize and validate a platelet-based factor VIII activity assay with greater
sensitivity to clinically important inhibitory antibodies.
patients, to determine when inhibitory antibodies against factor VIII have developed, and to
evaluate the activity of engineered pharmaceutical factor VIII products. Factor VIII
activity has been measured with one and two-stage assays for more than fifty years. However,
all existing assays have major shortcomings that are recognized by the FDA, the
International Society for Thrombosis and Haemostasis, and pharmaceutical companies. The
major deficiencies that have been identified are: 1) Factor VIII activity levels do not
predict the risk of bleeding in patients with inhibitory antibodies. The degree of
inhibition in these assays is less than required to explain patient bleeding. 2) The assays
are only accurate over a range of 1 - 100% of normal factor VIII activity, while values of
0.1 - 1% are also clinically important. 3) The different approved assays give discrepant
values for recombinant pharmaceutical factor VIII products, with a range of 2-fold
difference between assays. This can lead to clinically important differences in dosing of
factor VIII products from one region to another with corresponding risk of thrombosis or
bleeding.
The preliminary data identify an additional deficiency of commercial assays that has not
been anticipated. Commercial one and two-stage assays may not detect some clinically
significant inhibitor antibodies. Thus, the purpose of the proposed studies is to
standardize and validate a platelet-based factor VIII activity assay with greater
sensitivity to clinically important inhibitory antibodies.
Inclusion Criteria:
- hemophilia A
- presence of inhibitory antibodies
Exclusion Criteria:
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