Rescue Immunotolerance Study in Induction of Immune Tolerance (ITI)-Experienced Patients (RES.I.S.T. Experienced) (RESIST EXP)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Charta Fondazione Grant Provided by
Grifols Biologicals Inc.
CSL Behring
Biotest Pharmaceuticals Corporation
City of Hope Grant Provided by
Grifols Therapeutics Inc. (Talecris Biotherapeutics)
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01051076
First received: January 15, 2010
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Severe Hemophilia A
Drug: VWF/FVIII concentrates

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Complete success is the abolition of the inhibitor to < 0.6 BU, within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hours, measured after a 72-hour washout period. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Absence of relapse up to 12 months after achievement of tolerance. [ Time Frame: Up to 45 months ] [ Designated as safety issue: Yes ]
  • Time to achieve success- either partial or complete. [ Time Frame: 33 months ] [ Designated as safety issue: Yes ]
  • Safety - assessment of adverse events through treatment and compliance with prolonged regimen. [ Time Frame: 33 months ] [ Designated as safety issue: Yes ]
  • Cost of care. [ Time Frame: Up to 45 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: June 2009
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Factor VIII and von Willebrand Factor Drug: VWF/FVIII concentrates
200 IU/Kg by one or two bolus injections daily. After successful confirmation the dose will be tailed off progressively until discontinuation. Patients will be treated with a VWF/FVIII concentrates according to physician/patients preference.
Other Names:
  • Koate-DVI
  • Emoclot DI
  • Factane
  • 8Y
  • Optivate
  • Alphanate
  • Fahndi
  • Haemate P
  • Humate P
  • Haemoctine SDH
  • Octanate
  • Wilate

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  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: NCT01051076

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Charta Fondazione Grant Provided by
Grifols Biologicals Inc.
CSL Behring
Biotest Pharmaceuticals Corporation
City of Hope Grant Provided by
Grifols Therapeutics Inc. (Talecris Biotherapeutics)
Investigators
Principal Investigator: Nadia P. Ewing, MD Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010
  More Information

Additional Information:
Publications:
Bentorp E, Ekman M, Gunnarson M. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations Haemophilia 1996; 2: 95-99.
Kreuz W, Steiner J, Auerswald G, Beeg T, Becker S. Successful immunetolerance therapy of FVIII-inhibitor in chldren after changing from high to intermediate purity FVIII concentrate. Ann Hematol 1996; 72 (suppl 1).

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01051076     History of Changes
Other Study ID Numbers: 06200, 2008-007019-33
Study First Received: January 15, 2010
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board
Italy: Ethics Committee
Italy: National Bioethics Committee
Italy: The Italian Medicines Agency

Keywords provided by City of Hope Medical Center:
ITI
Haemophilia A
Inhibitors
Failed ITI
VWF/FVIII concentrates

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

ClinicalTrials.gov processed this record on October 23, 2014