Improved Factor VIII Inhibitor Evaluation

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

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

, ,

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

, ,

Verification Date

March 2016