Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A

Brief Title

Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A

Official Title

Advate Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (ADVATE rAHF-PFM): A Phase 4 Study Comparing Two Prophylactic Regimens in Subjects With Severe or Moderately Severe Hemophilia A

Brief Summary

      The primary purpose of this randomized, two-arm parallel clinical study in 66 previously
      treated patients with severe or moderately severe hemophilia A is to compare the rate of
      bleeding episodes for standard prophylaxis (20-40 IU/kg every 48 ± 6 hours; actual dose
      determined by the investigator) with that of alternate prophylaxis (20-80 IU/kg every 72 + 6
      hours; actual dose determined by Baxter utilizing an algorithm and the patient's
      pharmacokinetic data). The rates of bleeding episodes for the on-demand regimen and the
      prophylaxis regimens will also be compared for the cross-over portion of the study. Enrolled
      patients will be treated originally on demand for a period of 6 months and then they will be
      randomized into one of the prophylaxis arms. Prophylactic treatment will last for a period of
      12 months +/- 2 weeks.

Study Phase

Phase 4

Study Type

Interventional

Primary Outcome

Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens

Secondary Outcome

 Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens

Condition

Hemophilia A

Intervention

Antihemophilic factor, recombinant, manufactured protein-free

Study Arms / Comparison Groups

Description:  Standard prophylaxis

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

January 2006

Completion Date

June 2010

Primary Completion Date

June 2010

Eligibility Criteria

        Inclusion Criteria:

          -  The subject has severe or moderately severe hemophilia A as defined by a baseline
             factor VIII level <= 2% of normal, as tested at screening

          -  The subject has a documented history of at least 150 exposure days to factor VIII
             concentrates (either plasma-derived or recombinant)

          -  The subject is within 7 to 65 years of age

          -  The subject has a Karnofsky performance score > (greater than) 60

          -  The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4
             count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)

          -  The subject has been on a documented on-demand treatment regimen for at least 12
             months immediately prior to enrollment

          -  The subject has a documented history (e.g. in medical charts or dispensing
             information, or signed investigator statement) of at least 8 joint hemorrhages in the
             12 months immediately prior to enrollment

          -  The subject resides within the coverage area of the mobile compliance device; coverage
             area will be determined at screening

          -  The subject or the subject's legally authorized representative has provided written
             informed consent

        Exclusion Criteria:

          -  The subject has a known hypersensitivity to factor VIII concentrates or mouse or
             hamster proteins

          -  The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by
             Bethesda or Nijmegen assay) at any time prior to screening

          -  The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4
             BU (by Nijmegen Assay) in the central laboratory

          -  The subject has severe chronic liver disease as evidenced by, but not limited to, any
             of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal
             vein hypertension including presence of otherwise unexplained splenomegaly and history
             of esophageal varices.

          -  The subject has been diagnosed with an inherited or acquired hemostatic defect other
             than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease)

          -  The subject has been treated during the last sixty (60) days prior to or is being
             treated at screening/enrollment with an immunomodulating drug.

          -  The subject has participated in another investigational study within thirty (30) days
             of enrollment

          -  The subject has previously participated in a clinical study with rAHF-PFM

          -  The subject's clinical condition may require a major surgery (defined as moderate to
             critical risk and perioperative blood loss ≥ 500 mL) during the period of the
             subject's participation in the study

          -  The subject is female of childbearing potential with a positive pregnancy test

Gender

All

Ages

7 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Peter Collins, MD, ,

Location Countries

Austria

Location Countries

Austria

Administrative Informations

NCT ID

NCT00243386

Organization ID

Responsible Party

Sponsor

Study Sponsor

Baxalta now part of Shire

Study Sponsor

Peter Collins, MD, Principal Investigator, Cardiff and Vale NHS

Verification Date

October 2012