Primary Objectives:- Evaluate changes in the immune system upon exposure to FVIII in patients with severe hemophilia A - Identify immunologic predictors of FVIII inhibitor development or tolerance
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
An inhibitor is defined by a Nijmegen test > 0.6 Bethesda units (BU) on two
consecutive tests conducted in the central laboratory.
During the first 50 days of exposure to a single FVIII product:
- Analyze and quantify subclasses of anti-FVIII antibodies
- Characterize FVIII-specific T-cells and changes which occur
- Quantify total FOXP3-positive regulatory T-cells (Treg)
- Assess RNA expression, transcript profile, and exon usage in relevant pathways
- Identify F8 gene mutation and other known genomic predictors of inhibitor
development
- Record infection(s), immunization(s), bleeding episodes, and factor usage
Secondary outcome
N.a.
Background summary
Hemophilia A is a congenital bleeding disorder caused by deficiency of factor
VIII (FVIII) and is treated by replacement therapy with FVIII concentrate. The
prevention and treatment of bleeding symptoms is confounded by the development
of FVIII neutralizing antibodies, or inhibitors, in approximately 30% of
patients with severe hemophilia after exposure to FVIII concentrate. Patients
with inhibitors have substantially increased morbidity and increased cost of
care. Individual and environmental risk factors for inhibitor formation have
been identified, but more information is required before prediction models and
prevention strategies can be developed. Furthermore, mechanisms of inhibitor
formation and conversely, tolerance to FVIII among patients with hemophilia who
do not develop inhibitors, are poorly understood, limiting the ability to
develop rational therapies to overcome inhibitors.
The purpose of the HIPS study is to prospectively evaluate changes in immunity
upon exposure to FVIII in patients with severe hemophilia A, and identify
immunologic predictors of FVIII inhibitor development or tolerance. The
underlying premise of this study is that the type of FVIII-specific T-cell that
is activated during the first days of exposure to FVIII determines whether the
immune system will develop tolerance to FVIII or develop FVIII inhibitors.
Study objective
Primary Objectives:
- Evaluate changes in the immune system upon exposure to FVIII in patients with
severe hemophilia A
- Identify immunologic predictors of FVIII inhibitor development or tolerance
Study design
This is a multinational, multicenter, observational study to evaluate the
changes in immunity upon exposure to FVIII in patients with severe hemophilia A
previously untreated with factor concentrates. A single source of recombinant
FVIII will be used (Advate) and treatment is at the discretion of the
investigator. Subjects will be evaluated for 50 days of exposure to FVIII
treatment, or three years, whichever comes first. An exposure day is defined
as a calendar day during which one or more infusions of FVIII are given.
Study burden and risks
The research question is group related, there is a neglactable risk en minimal
burden.
It is important to include children in this study because the research
question concerns inhibitor development in hemophilia A, a complication that
occurs in the first years of life.
Travis Street 6655
Housten, Texas 77030
US
Travis Street 6655
Housten, Texas 77030
US
Listed location countries
Age
Inclusion criteria
1. An informed consent, approved by the appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC), has been administered, signed, and dated.
2. Subject has severe hemophilia A defined by a baseline FVIII:C <0.01 IU/ml. His FVIII activity will be confirmed at the central laboratory. If the confirmatory level is >=0.01 IU/ml the child must exit the study.
3. Subject weighs 3.5 kg or more at the time of his baseline study evaluation
Exclusion criteria
1. Subject has had prior exposure to clotting factor concentrates or blood products, including packed red blood cells (RBC), platelets, plasma, or cryoprecipitate.
2. Subject has a clinically significant chronic disease other than hemophilia A.
3. Subject is currently participating in another investigational drug study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42464.018.12 |