Improved Factor VIII Inhibitor Evaluation

NCT ID: NCT02726139

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-07-15
• Study Completion Date: 2021-01-25

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.

Conditions

Hemophilia; Hemophilia A

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Emory University

Samples obtained at and shipped from Emory University

No interventions assigned to this group

University of Michigan

Samples obtained at and shipped from University of Michigan

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• hemophilia A
• presence of inhibitory antibodies

Exclusion Criteria

• none

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Boston VA Research Institute, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Boston VA Research Institute (BVARI)

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

BVARI_GG_2016_1

Identifier Type: -

Identifier Source: org_study_id