Study Comparing On-Demand Treatment With Two Prophylaxis Regimens Of BeneFIX In Patients With Severe Hemophilia B
Condition: Hemophilia B
MeSH terms: Hemophilia A; Hemophilia B
Intervention: Recombinant Coagulation Factor IX (BeneFIX); Recombinant Coagulation Factor IX (BeneFIX)
Intervention description: 100 IU/kg once weekly then crossover to 50 IU/kg twice weekly; 50 IU/kg twice weekly then crossover to 100 IU/kg once weekly
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: Male
Minimum age: 6 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hemophilia B; BeneFIX

Summary:

      This study is designed to evaluate BeneFIX infused as prophylaxis regimens, compared with
      BeneFIX administered as an on-demand regimen only. In the trial, subjects will participate in
      4 study periods. The first period is a 16-week on-demand treatment, during which subjects
      will utilize BeneFIX to treat bleeding events episodically only as they occur (i.e.,
      on-demand treatment). At the end of this period, subjects will be randomly assigned to 1 of 2
      BeneFIX prophylaxis regimens: either 100 IU/kg once weekly or 50 IU/kg twice weekly, and
      followed for 16 weeks. At the end of this period, subjects will use on-demand treatment for 8
      weeks. The purpose of this 8-week period is to mitigate the potential carry-over effect of
      the prior prophylaxis regimen on bleeding frequency. Following this 8-week on-demand
      treatment, subjects will cross-over and receive the alternate study prophylactic regimen for
      16 weeks.

      The primary endpoint is annualized number of bleeding episodes, compared between the first
      on-demand period and each of the prophylaxis regimens. A comparison of annualized bleeding
      episodes between the two prophylaxis regimens will also be performed. Subject-reported
      outcomes will also be collected using a patient diary. At 24 and 48 hours following the onset
      of each joint bleeding episode, information on pain, sleep, and work will be collected.
      Additional data on physical functioning will be recorded on the diary at the end of the
      16-week on-demand period, and at the end of each prophylaxis period. Information on safety
      will also be collected.

      Each subject will participate in this study for approximately 59 weeks (15 months), including
      a screening period of up to 3 weeks, an initial 16-week on-demand period, two prophylaxis
      treatment periods of 16 weeks each, separated by an 8-week on-demand treatment period.

      A modified FIX recovery study will be performed once during each prophylaxis period.

      The study diary will also be used by subjects to collect secondary endpoints. These
      endpoints, which are subject-reported outcomes, will be recorded in the diary at 24 and 48
      hours following the onset of each joint bleeding episode. Additional data on physical
      functioning will be recorded on the diary at the end of the 16-week on-demand period, and at
      the end of each prophylaxis period.

      Patients will be recruited in the United States, Canada, Europe and Russia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented history of moderately severe or severe hemophilia B (FIX:C less than or
             equal to 2%)

          -  Male subjects, aged 6 years to 65 years.

          -  Subjects with a minimum of 12 bleeding episodes, 6 of which must be joint bleeds, in
             the 12 months before screening.

        Exclusion Criteria:

          -  Subjects currently utilizing FIX primary prophylaxis.

          -  Subjects with HIV+ who have a CD4 count less than 200

          -  Subjects with hepatic or renal impairment.

          -  Prothrombin time or International Normalized Ration more than 1.5 times the upper
             limit of normal.

          -  Major surgery or an orthopedic surgical procedure within the past 3 months or is
             planned within the duration of participation in this study.

          -  Past history of, or current FIX inhibitor.

          -  Hypersensitivity to any FIX product or hamster protein.

          -  Exposure to any investigational drug, except for rFIX-R, or device within 30 days of
             providing consent/assent (as appropriate) for this study.

          -  Bleeding disorders other than hemophilia B.

          -  Concurrent inflammatory disease that in the investigator's judgment could confound the
             study results.