Improved Factor VIII Inhibitor Evaluation (IFIE)

February 23, 2021 updated by: Boston VA Research Institute, Inc.
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

Study Overview

Status

Withdrawn

Conditions

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • Boston VA Research Institute (BVARI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

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

Description

Inclusion Criteria:

  • hemophilia A
  • presence of inhibitory antibodies

Exclusion Criteria:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Emory University
Samples obtained at and shipped from Emory University
University of Michigan
Samples obtained at and shipped from University of Michigan

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston VA Research Institute, Inc.

Collaborators

University of Michigan
Emory University
Shire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2016

Primary Completion (Actual)

January 25, 2021

Study Completion (Actual)

January 25, 2021

Study Registration Dates

First Submitted

March 29, 2016

First Submitted That Met QC Criteria

March 31, 2016

First Posted (Estimate)

April 1, 2016

Study Record Updates

Last Update Posted (Actual)

February 25, 2021

Last Update Submitted That Met QC Criteria

February 23, 2021

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BVARI_GG_2016_1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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