Improved Factor VIII Inhibitor Evaluation

Withdrawn

• Conditions: Hemophilia A; Hemophilia

• Registration Number: NCT02726139
• Lead Sponsor: Boston VA Research Institute, Inc.

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 Timeline

• Status Verified: 2016-03
• Study First Submitted: 2016-03-29
• Study First Submitted QC: 2016-03-31
• Study First Posted: 2016-04-01
• Study Start: 2016-07-15
• Primary Completion: 2021-01-25
• Study Completion: 2021-01-25
• Last Update Submitted: 2021-02-23
• Last Update Posted: 2021-02-25

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

• hemophilia A
• presence of inhibitory antibodies

Exclusion Criteria

• none

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Bleeding exceeds risk predicted by factor VIII assay	1 year	annual bleeding rate exceeds the rate predicted from the residual factor VIII activity
Bleeding is in accord with the risk assigned by platelet-dependent factor VIII activity	1 year	annual bleeding rate is within the predicted range from residual factor VIII activity

Trial Locations

Locations (1)

Boston VA Research Institute (BVARI); 🇺🇸 Boston, Massachusetts, United States