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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00364182
First received: August 14, 2006
Last updated: August 30, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Hemophilia B
Drug: Recombinant Coagulation Factor IX (BeneFIX)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Annualized Number of Bleeding Episodes [ Time Frame: Baseline up to Week 56 ] [ Designated as safety issue: No ]
    Annualized bleed rate (ABR) or number of bleeds per year derived for each participant for each treatment regimen by using the following formula: ABR = number of bleeds / (days on treatment regimen / 365.25)


Secondary Outcome Measures:
  • Amount of Sleep Measured by Sleep Diary After Hemarthrosis [ Time Frame: 24 and 48 hours post-bleed ] [ Designated as safety issue: No ]
    For each bleeding event, a diary was filled out that night and the subsequent night. Questions included: How long do you think you slept last night? Reported as average duration of sleep during study.

  • Quality of Sleep Measured by Sleep Diary After Hemarthrosis [ Time Frame: 24 and 48 hours post-bleed ] [ Designated as safety issue: No ]
    For each bleeding event, a diary was filled out that night and the subsequent night. Questions included: How would you describe the quality of your sleep last night? 1=Very Good, 2=Good, 3=Fair, 4=Poor, 5=Very Poor. Reported as quality of sleep during study.

  • Acute Pain After Hemarthrosis [ Time Frame: 24 and 48 hours post-bleed ] [ Designated as safety issue: No ]
    For each bleeding event, a diary was filled out that night and the subsequent night and included a Brief Pain Inventory (BPI): self-reported scale that measured severity of pain experienced over the past 24 hours. Questions included How much pain right now? 0 (no pain) to 10 (pain as severe as you can imagine).

  • Health-Related Productivity Questionnaire (HRPQ) Score: Hours Lost From Work or School at 24 Hours Post-bleed [ Time Frame: 24 hours post-bleed ] [ Designated as safety issue: No ]
    HRPQ: self-reported scale that measured for each bleed event, hours lost from work, school and housework because of hemophilia and its treatments. Mean and standard deviations calculated from measured values.

  • HRPQ Score: Hours Lost From Work or School at 48 Hours Post-bleed [ Time Frame: 48 hours post-bleed ] [ Designated as safety issue: No ]
    HRPQ: self-reported scale that measured for each bleed event, hours lost from work, school and housework because of hemophilia and its treatments. Mean and standard deviations calculated from measured values.

  • 36-Item Short-Form Health Survey (SF-36): Physical Functioning Domain [ Time Frame: Weeks 16, 32, and 56 ] [ Designated as safety issue: No ]
    SF-36: standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The physical functioning domain score was an average of the individual physical functioning question scores across all time points, which was scaled 0-100 (100=highest level of functioning).


Enrollment: 50
Study Start Date: May 2007
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Recombinant Coagulation Factor IX (BeneFIX)
100 IU/kg once weekly then crossover to 50 IU/kg twice weekly
Experimental: B Drug: Recombinant Coagulation Factor IX (BeneFIX)
50 IU/kg twice weekly then crossover to 100 IU/kg once weekly

  Eligibility

Ages Eligible for Study:   6 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364182

Locations
United States, Arizona
Pfizer Investigational Site
Phoenix, Arizona, United States, 85016
United States, Illinois
Pfizer Investigational Site
Chicago, Illinois, United States, 60614
Pfizer Investigational Site
Chicago, Illinois, United States, 60612-3833
United States, New Jersey
Pfizer Investigational Site
New Brunswick, New Jersey, United States, 08903-0019
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030-4009
Canada, Alberta
Pfizer Investigational Site
Edmonton, Alberta, Canada, T6G 2C8
Pfizer Investigational Site
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Pfizer Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
Croatia
Pfizer Investigational Site
Zagreb, Croatia, 10000
Hungary
Pfizer Investigational Site
Budapest, Hungary, 1134
Italy
Pfizer Investigational Site
Castelfranco Veneto (TV), Italy, 31033
Pfizer Investigational Site
Coppito (AQ), Italy, 67100
Romania
Pfizer Investigational Site
Bucuresti, Romania, 011155
Russian Federation
Pfizer Investigational Site
Moscow, Russian Federation, 125167
Pfizer Investigational Site
Saint Petersburg, Russian Federation, 191186
Serbia
Pfizer Investigational Site
Belgrade, Serbia, 11000
Pfizer Investigational Site
Nis, Serbia, 18000
Spain
Pfizer Investigational Site
Madrid, Spain, 28046
Pfizer Investigational Site
Sevilla, Spain, 41013
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00364182     History of Changes
Other Study ID Numbers: 3090A1-400, B1821002
Study First Received: August 14, 2006
Results First Received: July 25, 2011
Last Updated: August 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Hemophilia B
BeneFIX

Additional relevant MeSH terms:
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on September 18, 2014