Clinical trial NCT02726139: Improved Factor VIII Inhibitor Evaluation
Official title: Improved Factor VIII Inhibitor Evaluation
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Hemophilia
Hemophilia A
Keywords: Factor VIII
inhibitor
assay
Lead sponsor: Boston VA Research Institute, Inc.
Sponsor class: OTHER
Collaborators: name: Shire
name: Emory University
name: University of Michigan
First posted: 2016-04-01
Enrollment: 0
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hemophilia A and inhibitory antibodies that have agreed to store plasma and prospectively consented to testing to evaluate bleeding mechanism

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.

Eligibility criteria: Inclusion Criteria:

* hemophilia A
* presence of inhibitory antibodies

Exclusion Criteria:

* none

Primary outcomes:
measure: Bleeding exceeds risk predicted by factor VIII assay
timeFrame: 1 year
measure: Bleeding is in accord with the risk assigned by platelet-dependent factor VIII activity
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston VA Research Institute (BVARI)
state: Massachusetts
Study officials:
References: