Study Comparing On-Demand Treatment With Two Prophylaxis Regimens Of BeneFIX In Patients With Severe Hemophilia B

A Multicenter, Open-Label Study To Compare On-Demand Treatment With 2 Prophylaxis Regimens of Recombinant Coagulation Factor IX (BeneFIX) Reformulated Drug Product (rFIX-R) In Subjects With Severe Hemophilia B

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.

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.