Brief Title
Improved Factor VIII Inhibitor Evaluation
Official Title
Improved Factor VIII Inhibitor Evaluation
Brief Summary
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
Detailed Description
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.
Study Type
Observational
Primary Outcome
Bleeding exceeds risk predicted by factor VIII assay
Condition
Hemophilia
Study Arms / Comparison Groups
Emory University
Description: Samples obtained at and shipped from Emory University
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
0
Start Date
July 15, 2016
Completion Date
January 25, 2021
Primary Completion Date
January 25, 2021
Eligibility Criteria
Inclusion Criteria: - hemophilia A - presence of inhibitory antibodies Exclusion Criteria: - none
Gender
Male
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02726139
Organization ID
BVARI_GG_2016_1
Responsible Party
Sponsor
Study Sponsor
Boston VA Research Institute, Inc.
Collaborators
Shire
Study Sponsor
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Verification Date
March 2016