Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B

Study Overview
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Brief Summary
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The purpose of this study will be to determine if a once-weekly prophylaxis regimen of BeneFIX in subjects with moderately severe to severe Hemophilia B is safe and effective.

Official Title
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A Multicenter, Open-label Study To Compare On-demand Treatment To A Prophylaxis Regimen Of Nonacog-alfa (Benefix) In Subjects With Moderately Severe To Severe Hemophilia B (Fix:c</=2%)

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: Nonacog alfa
* Biological: Nonacog alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of moderately-severe to severe hemophilia B (FIX activity </=2%). Male subjects, aged 12 years to 65 years. Subjects with at least 100 exposure days (EDs) to factor IX products. Subjects with a minimum of 12 bleeding episodes, 6 of which must be joint bleeds, in the 12-month period before the Screening visit. Exclusion Criteria: Subjects who have received FIX as a primary or secondary prophylaxis regimen within the last 12 months prior to the Screening visit. Subjects who have had major surgery or an orthopedic surgical procedure within the past 3 months prior to Screening visit. Subjects for which major surgery or orthopedic surgery is planned within the duration of study participation. Subjects with a past history of, or current FIX inhibitor, defined as >ULN (upper limit of normal) of the reporting laboratory. Subjects with a known hypersensitivity to any FIX product or hamster protein.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: BeneFIX<br> | Biological: Nonacog alfa<br>* Period 1: During on-demand period, dosing at the discretion of investigator.<br>* Other names: BeneFIX;Biological: Nonacog alfa<br>* Period 2: During the prophylaxis period, 100 IU/kg once weekly<br>* Other names: BeneFIX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Number of Bleeding Episodes. | The annualized bleed rate (ABR) or the annualized number of bleeding episodes per year, will be derived for each participant for each treatment period by using the following formula: ABR = number of bleeds / (Days on treatment period / 365.25) The number of bleeds for the ABR calculation includes all bleeds requiring treatment with factor IX product during the time on treatment. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to On-Demand Treatment for All Bleeding Episodes. | Assessment scores on a 4-point Response Scale for an on-demand bleeding episode, as assessed by participant/caregiver or investigator/qualified staff. The 4-point scale assessments are Excellent, Good, Moderate or No response. Responses to number of observations were noted. | 2 years | 
| Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. | The number of study drug infusions administered to treat a bleed will be calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time). The number of infusions needed to treat a bleed will be classified into the following categories: 1, 2, 3, 4 and >4 infusions. If there were more than one bleed location (e.g., ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence. | 2 years | 
| Number of Breakthrough (Spontaneous/Non-Traumatic) Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX. | The number of spontaneous, non-traumatic breakthrough bleeds within 48 hours following a prophylaxis dose of BeneFIX were summarized. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence. | 2 years | 
| Average Infusion Dose. | The mean dose by per infusion by weight (IU/kg) was reported for both prophylaxis and on demand infusions | 2 years | 
| Total Factor Consumption. | The total amount (IU) infused for each infusion recorded were summed to calculate the total factor consumption for each participant. For each infusion, IU/kg was calculated, using the most recently recorded weight measurement and the total factor consumption, divided by number of infusions, and was summarized similarly to average infusion dose (IU). Annualized TFC by weight was reported. Annualized TFC by weight = (Total IU/kg / treatment interval duration)*365.25. | 2 years | 
| Incidence of Less Than Expected Therapeutic Effect (LETE) | The following criteria are the definitions for LETE in this study: 1. LETE in the On-Demand Setting: LETE occurs in the on-demand setting if 2 successive No Response ratings are recorded after 2 successive BeneFIX drug infusions in the absence of confounding factors. 2. LETE in the Prophylaxis Setting: LETE occurs in the prophylaxis setting if there is a spontaneous bleed within 48 hours (≤ 48 hours) after a regularly scheduled prophylactic dose of BeneFIX in the absence of confounding factors. 3. LETE (Low Recovery): LETE can also be lower than expected recovery of FIX in the opinion of the investigator following infusion of BeneFIX in the absence of confounding factors. Each reported occurrence of low recovery LETE was listed. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonacog alfa, Hemophilia B, on-demand, prophylaxis, BeneFIX, FIX