Hemophilia Inhibitor Genetics Study (HIGS)

Completed

• Conditions: Hemophilia A With Inhibitor
• Interventions: Procedure: Blood draw

• Registration Number: NCT00166387
• Lead Sponsor: Skane University Hospital

Brief Summary

Several non-genetic and genetic factors that could influence the risk of inhibitor development in hemophilia A have been discussed but not fully explored. The aim of the HIGS is to identify these genetic factors.

Detailed Description

The objective of the HIGS is to determine host genetic factors, other than mutations within the factor VIII gene, that are associated with the development of inhibitors in severe hemophilia A and response to antigenic challenge by factor VIII. The study will involve three phases, enrolling family groups composed of brother pairs and their parents (Phase I) and siblings, a family group composed of a person with severe hemophilia and his parents (Phase II), and a group of unrelated people with severe hemophilia for the purpose of confirming associations identified in Phases I and II.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-14
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-24
• Last Update Posted: 2014-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1137

Inclusion Criteria

• Severe hemophilia A is defined as a baseline factor VIII level <1%. A history of inhibitor is defined as ever having a Bethesda titer > 1 BU.

Phase I.

Subjects with hemophilia are eligible for Phase I of the study if all of the following apply:

• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject has severe hemophilia A.
• The subject has a history of inhibitor or the subject has no history of inhibitor but has at least 100 exposure days to factor VIII products.
• Sufficient documentation exists to identify the subject's maximum lifetime Bethesda titer.
• The subject has a history of inhibitor and has one or more full brothers with severe hemophilia A, with or without an inhibitor, who are eligible for and have agreed to be in the study, and two parents who have agreed to be in the study or the subject does not have a history of inhibitor but has one or more full brothers with severe hemophilia A and a history of inhibitor who are eligible for and have agreed to be in the study, and two parents who have agreed to be in the study.

Subjects without hemophilia are eligible for Phase I of the study if all of the following apply:

• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject is the parent (mother or father) of, or the full sibling of, a subject with hemophilia who is eligible for Phase I of the study.

Phase II.

Subjects with hemophilia are eligible for Phase II of the study if all of the following apply:

• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject has severe hemophilia A.
• The subject has a history of inhibitor and two parents who have agreed to be in the study.
• Sufficient documentation exists to identify the subject's maximum lifetime Bethesda titer.

Subjects without hemophilia are eligible for Phase II of the study if all of the following apply:

• An informed consent form, approved by the appropriate IRB/IEC, has been administered, signed, and dated.
• The subject is the parent (mother or father) of a subject with hemophilia who is eligible for Phase II of the study.

Exclusion Criteria

Phase I.

Subjects (with or without hemophilia) are excluded from participation in Phase I if:

• The minimum family group, defined as a pair of full brothers with hemophilia, either concordant (both with) or discordant (one with, one without) for inhibitor, and both of their parents, is not enrolled.

Phase II.

Subjects are excluded from participation in Phase II if:

• The minimum family group, defined as a person with hemophilia and a history of inhibitor and his mother and father, is not enrolled.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Phase I, II, III	Blood draw	Phase I consists of a brother pair with hemophilia, one or both of whom has a history of inhibitors, and their parents; Phase II consists of a person with hemophilia and an inhibitor, and both his parents; Phase III consists of an unrelated group of people with hemophilia.

Primary Outcome Measures

Name	Time	Method
development of inhibitory antibodies to factor VIII	upon development of inhibitor or following at least 100 exposure days to factor VIII

Trial Locations

Locations (1)

Malmo University Hospital; 🇸🇪 Malmo, Sweden