Hemophilia Inhibitor Genetics Study (HIGS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,137
- 试验地点
- 1
- 主要终点
- development of inhibitory antibodies to factor VIII
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
- •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.
排除标准
- •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.
- •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.
结局指标
主要结局
development of inhibitory antibodies to factor VIII
时间窗: upon development of inhibitor or following at least 100 exposure days to factor VIII
次要结局
未报告次要终点
研究者
Sharyne M. Donfield, Ph.D.
Professor Erik Berntorp, Malmö University Hospital
Skane University Hospital