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International Immune Tolerance Study

This study has been terminated.
(The DSMB recommended stopping the study due to safety concerns.)
Sponsor:
Collaborator:
Central Manchester University Hospitals NHS Foundation Trust
Information provided by:
New York Presbyterian Hospital
ClinicalTrials.gov Identifier:
NCT00212472
First received: September 13, 2005
Last updated: December 4, 2009
Last verified: October 2009
History of Changes
  Purpose
The purpose of this study is to see if a low-dose arm or a high dose-arm of immune tolerance is more effective in eliminating inhibitors in patients with hemophilia A.

Condition Intervention
Hemophilia A With Inhibitors
 Drug: Factor VIII concentrates
Other: Low-dose treatment
Other: High-dose treatment

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An International Randomised Controlled Trial Of Immune Tolerance Induction

Resource links provided by NLM:

MedlinePlus related topics: Hemophilia
U.S. FDA Resources

Further study details as provided by New York Presbyterian Hospital:

Primary Outcome Measures:
  • Success-rate and partial success-rate [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The time from the start of ITI to successful tolerance [ Time Frame: Up to 33 months ] [ Designated as safety issue: No ]
  • The comparative cost-effectiveness of the two treatment arms [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI. [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The dose-regimen, success rate and time to ITI, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The starting inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The peak historical inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The peak inhibitor titre after starting ITI, success rate and time to success, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The age at the time of inhibitor detection, success-rate and time to success, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI. [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The effect of interim infections/immunisations, success rate and time to success, [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
  • The effect of treatment interruption, success rate and time to success. [ Time Frame: Up to 69 months ] [ Designated as safety issue: No ]
Enrollment: 134
Study Start Date: July 2002
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:
Subjects will be randomized into a low-dose or high-dose immune tolerance regimen and this study will compare the success rates, the time to achieve tolerance,the complications and the cost of both regimens.It will also aim to identify predictors of successful immune tolerance.
  Eligibility
Ages Eligible for Study:   up to 7 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00212472

  Show 39 Study Locations
Sponsors and Collaborators
New York Presbyterian Hospital
Central Manchester University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Donna M DiMichele, MD Weill Cornell Medical College-NY Presybetrian Hospital
Principal Investigator: Charles Hay, MD Manchester Royal Infirmary
  More Information

Responsible Party: Donna DiMichele, MD, New York Presbyterian Hospital
ClinicalTrials.gov Identifier: NCT00212472     History of Changes
Other Study ID Numbers: ITI 
Study First Received: September 13, 2005
Last Updated: December 4, 2009
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
 Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants

ClinicalTrials.gov processed this record on September 23, 2016