Brief Title
Rescue Immunotolerance Study in Induction of Immune Tolerance (ITI)-Experienced Patients (RES.I.S.T. Experienced)
Official Title
Immune Tolerance Induction Study in Patients With Severe Type A Haemophilia With Inhibitor After Failure of a Previous Induction of Immune Tolerance With FVII Concentrates Without Von Willebrand Factor Rescue
Brief Summary
The purpose of this study is to evaluate whether a concentrate containing both FVIII and von Willebrand Factor (VWF) given at a high dose will induce immune tolerance in subjects who have already experienced and failed ITI with VWF-free FVIII concentrates. The treatment on this study is expected to last up to 33 months.
Detailed Description
The presence of Factor VIII (FVIII) inhibitor prevents FVIII infusions from working properly and makes treatment of bleeding episodes very difficult. Having an inhibitor is a serious and life-threatening complication in patients with Hemophilia. The usual treatment of patients with FVIII inhibitors involves what is called "immune tolerance induction" (ITI). Immune Tolerance means that the body can accept infused FVIII and that FVIII is again effective in controlling bleeds. ITI involves giving high doses of FVIII regularly until the inhibitor disappears. This treatment is not always effective. The inhibitor persists in about 1 in 5 patients who undergo ITI. There are 2 types of FVIII concentrates: FVIII concentrates derived from human plasma, which contain VWF, and concentrates of FVIII without VWF. Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies on subjects who were treated with VWF containing Factor VIII concentrates after failing ITI with pure factor VIII concentrates, have shown that tolerance can be achieved in a large percentage of patients. This study will access prospectively whether treatment with a FVIII concentrate containing VWF given at a high dose (200 units per kilogram) daily for up to 33 months is able to induce immune tolerance after previous attempts with concentrates containing only FVIII have failed.
Study Type
Interventional
Primary Outcome
Achievement of an inhibitor titer of <0.6 BU/failure to achieve an inhibitor titer of <0.6 BU within 33 months, or failure to decrease inhibitor titer by at least 20% compared to titer in prior 6 months, beginning at 3 months after starting ITI
Secondary Outcome
Time to achieve success- either partial or complete.
Condition
Severe Hemophilia A
Intervention
VWF/FVIII concentrates
Study Arms / Comparison Groups
Factor VIII and von Willebrand Factor
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
3
Start Date
November 3, 2009
Completion Date
October 21, 2020
Primary Completion Date
October 21, 2020
Eligibility Criteria
Inclusion Criteria: 1. severe hemophilia A (FVIII<1%) with high responding inhibitors (peak levels >5 BU) 2. male, any age; 3. any inhibitor level at study enrollment; 4. ability and willingness to participate to the study; 5. previous ITI course of at least 9 months with a VWF-free FVIII concentrate at any dosage, such as recombinant FVIII and/or monoclonally purified FVIII. Exclusion Criteria: 1. concomitant systemic treatment with immunosuppressive drugs; 2. concomitant experimental treatment; 3. previous history of myocardial infarction and/or cerebral stroke
Gender
Male
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Nadia P. Ewing, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01051076
Organization ID
06200
Secondary IDs
2008-007019-33
Responsible Party
Sponsor
Study Sponsor
City of Hope Medical Center
Collaborators
Charta Foundation
Study Sponsor
Nadia P. Ewing, MD, Principal Investigator, Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010
Verification Date
December 2020