International Immune Tolerance Study
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ClinicalTrials.gov Identifier: NCT00212472 |
Recruitment Status :
Terminated
(The DSMB recommended stopping the study due to safety concerns.)
First Posted : September 21, 2005
Last Update Posted : December 7, 2009
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hemophilia A With Inhibitors | Drug: Factor VIII concentrates Other: Low-dose treatment Other: High-dose treatment | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 134 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | An International Randomised Controlled Trial Of Immune Tolerance Induction |
Study Start Date : | July 2002 |
Estimated Primary Completion Date : | December 2010 |
Estimated Study Completion Date : | December 2012 |

Arm | Intervention/treatment |
---|---|
Active Comparator: 1
Low-dose treatment (50 FVIII u/kg three times a week).
|
Drug: Factor VIII concentrates
To be determined at the discretion of the investigator. Other: Low-dose treatment 50 FVIII u/kg three times a week. |
Active Comparator: 2
High-dose treatment (200 FVIII u/kg per day).
|
Drug: Factor VIII concentrates
To be determined at the discretion of the investigator. Other: High-dose treatment 200 FVIII u/kg per day. |
- Success-rate and partial success-rate [ Time Frame: Up to 69 months ]
- The time from the start of ITI to successful tolerance [ Time Frame: Up to 33 months ]
- The comparative cost-effectiveness of the two treatment arms [ Time Frame: Up to 69 months ]
- A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days. [ Time Frame: Up to 69 months ]
- The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI. [ Time Frame: Up to 45 months ]
- The dose-regimen, success rate and time to ITI, [ Time Frame: Up to 69 months ]
- The starting inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ]
- The peak historical inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ]
- The peak inhibitor titre after starting ITI, success rate and time to success, [ Time Frame: Up to 69 months ]
- The age at the time of inhibitor detection, success-rate and time to success, [ Time Frame: Up to 69 months ]
- The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI. [ Time Frame: Up to 69 months ]
- The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success, [ Time Frame: Up to 69 months ]
- The effect of interim infections/immunisations, success rate and time to success, [ Time Frame: Up to 69 months ]
- The effect of treatment interruption, success rate and time to success. [ Time Frame: Up to 69 months ]

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Ages Eligible for Study: | up to 7 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Severe hemophilia A (FVIII level <1%).
- A maximum historical inhibitor titer of between 5 BU and 200 BU that must be confirmed once prior to the beginning of ITI.
- The inhibitor titer should be <10 BU at the start of ITI, confirmed once.
- The inhibitor must be present for <24 months when ITI begins.
- Maximum age of 7 at the start of ITI.
- Willingness to comply with the protocol.
Exclusion Criteria:
- Moderate or mild hemophilia A (FVIII level >1%).
- Spontaneous disappearance of the inhibitor prior to ITI.
- Historical maximum inhibitor titer <5 BU or > 200 BU before starting ITI.
- Inhibitor titer > 10 BU at the start of ITI.
- Inhibitor present for more than 24 months before starting ITI.
- Systemic immunomodulatory drug therapy during immune tolerance e.g. corticosteroids (< 5 days every 2 months maximum dose 2 mg/kg or 60 mg/day), azathioprine, cyclophosphamide, high-dose immunoglobulin or the use of a protein A column or plasmapheresis.
- Age > 7 years at the start of ITI.
- Inability or unwillingness to comply with the protocol.
- Previous attempt at ITI.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00212472

Principal Investigator: | Donna M DiMichele, MD | Weill Cornell Medical College-NY Presybetrian Hospital | |
Principal Investigator: | Charles Hay, MD | Manchester Royal Infirmary |
Responsible Party: | Donna DiMichele, MD, New York Presbyterian Hospital |
ClinicalTrials.gov Identifier: | NCT00212472 |
Other Study ID Numbers: |
ITI |
First Posted: | September 21, 2005 Key Record Dates |
Last Update Posted: | December 7, 2009 |
Last Verified: | October 2009 |
Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders |
Hemorrhagic Disorders Genetic Diseases, Inborn Factor VIII Coagulants |