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

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

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

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