Hemophilia Inhibitor Genetics Study (HIGS)

Hemophilia A With Inhibitor Clinical Trial

Official title:

Hemophilia Inhibitor Genetics Study (HIGS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00166387
• Other study ID #: HIGS
• Status: Completed
• Phase: N/A
• First received: September 9, 2005
• Last updated: March 24, 2014
• Start date: April 2003
• Est. completion date: December 2013

Study information

• Verified date: March 2014
• Source: Skane University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1137
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Observational Model: Family-Based

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitor

Intervention

Procedure:
• Blood draw
A single blood draw.

Locations

Country	Name	City	State
Sweden	Malmo University Hospital	Malmo

Sponsors (1)

Lead Sponsor	Collaborator
Skane University Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Astermark J, Donfield SM, Gomperts ED, Schwarz J, Menius ED, Pavlova A, Oldenburg J, Kessing B, DiMichele DM, Shapiro AD, Winkler CA, Berntorp E; Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Blood. 2013 Feb 21;121(8):1446-54. doi: 10.1182/blood-2012-06-434803. Epub 2012 Dec 6. — View Citation

Berntorp E, Astermark J, Donfield SM, Nelson GW, Oldenburg J, Shapiro AD, Dimichele DM, Ewenstein BM, Gomperts ED, Winkler CA; Hemophilia Inhibitor Genetics Study. Haemophilia Inhibitor Genetics Study - evaluation of a model for studies of complex diseases using linkage and association methods. Haemophilia. 2005 Jul;11(4):427-9. — View Citation

Schwarz J, Astermark J, Menius ED, Carrington M, Donfield SM, Gomperts ED, Nelson GW, Oldenburg J, Pavlova A, Shapiro AD, Winkler CA, Berntorp E; Hemophilia Inhibitor Genetics Study Combined Cohort. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Haemophilia. 2013 Jan;19(1):113-8. doi: 10.1111/hae.12004. Epub 2012 Sep 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	development of inhibitory antibodies to factor VIII		upon development of inhibitor or following at least 100 exposure days to factor VIII	No