Study of First TIME Immunotolerance Induction in Severe Hemophilia A Patients With Inhibitor at High Risk of Failure: Comparison With FVIII Concentrates With or Without Von Willebrand Factor – RES.I.S.T. Naive

Brief Title

Study of First TIME Immunotolerance Induction in Severe Hemophilia A Patients With Inhibitor at High Risk of Failure: Comparison With FVIII Concentrates With or Without Von Willebrand Factor - RES.I.S.T. Naive

Official Title

Randomised Study of First TIME Immunotolerance Induction in Patients With Severe Type A Haemophilia With Inhibitor at High Risk of Failure: Comparison of Induction of Immune Tolerance With FVIII Concentrates With or Without Von Willebrand Factor Acronym: RES.I.S.T.- Naive

Brief Summary

      This is a prospective, controlled, randomized, open label study, aimed at comparing FVIII/VWF
      concentrates with FVIII concentrates at 200 IU/kg daily in their ability to induce immune
      tolerance in Haemophilia A patients with high responding inhibitors and poor prognosis for
      success.

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 "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 the von Willebrand factor, and concentrates of FVIII without VWF (recombinant or
      plasma derived). Both types of concentrates are commonly used to induce immune tolerance in
      patients with Hemophilia A. Retrospective studies in subjects with hemophilia and inhibitors
      at risk for failing ITI, have indicated a higher rate of success if patients were treated
      with von Willebrand containing factor VIII concentrates. It is not known whether the addition
      of Von Willebrand factor offers an advantage to achieving immune tolerance.

Study Type

Interventional

Primary Outcome

Primary end point is the success in inducing immune tolerance, defined as: the abolition of the inhibitor to < 0.6 BU within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hrs, and measured after a 72-hour washout period.

Secondary Outcome

 Absence of relapse, up to 12 months after achievement of Immune Tolerance

Condition

Severe Hemophilia A

Intervention

FVIII Concentrates

Study Arms / Comparison Groups

 von Willebrand factor-free FVIII concentrates

Description:  Patients treated with FVIII concentrates

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

September 25, 2009

Completion Date

June 25, 2020

Primary Completion Date

June 25, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. severe hemophilia A (FVIII<1%);

          2. male, any age;

          3. high responders (peak inhibitor levels > 5 BU);

          4. any inhibitor level at study enrolment;

          5. ability and willingness to participate in the study;

          6. at least one of the following risk factors for ITI failure:

               -  peak inhibitor titer > 200 BU

               -  titer at ITI start > 10 BU

               -  age > 7 years

               -  time between inhibitor occurrence and ITI > 2 years

          7. absence of high risk of cardiovascular, cerebrovascular or other thromboembolic events
             as deemed by the treating clinician.

        Exclusion Criteria:

          1. concomitant systemic treatment with immunosuppressive drugs;

          2. concomitant experimental treatment;

          3. previous ITI attempt;

          4. 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, ,

Administrative Informations

NCT ID

NCT01051544

Organization ID

Secondary IDs

2008-007016-15

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