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

• ClinicalTrials.gov Identifier: NCT01335061
• Recruitment Status: Completed
• First Posted: April 13, 2011
• Results First Posted: May 4, 2015
• Last Update Posted: June 8, 2015
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 30, 2011
• First Posted Date: April 13, 2011
• Results First Submitted Date: March 18, 2015
• Results First Posted Date: May 4, 2015
• Last Update Posted Date: June 8, 2015
• Study Start Date: September 2011
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2015)

Annualized Number of Bleeding Episodes. [ Time Frame: 2 years ]

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.

• Original Primary Outcome Measures (submitted: April 12, 2011): Annualized number of bleeding episodes [ Time Frame: Up to 2 years ]

Current Secondary Outcome Measures (submitted: April 30, 2015)

• Response to On-Demand Treatment for All Bleeding Episodes. [ Time Frame: 2 years ]
  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.
• Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. [ Time Frame: 2 years ]
  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.
• Number of Breakthrough (Spontaneous/Non-Traumatic) Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX. [ Time Frame: 2 years ]
  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.
• Average Infusion Dose. [ Time Frame: 2 years ]
  The mean dose by per infusion by weight (IU/kg) was reported for both prophylaxis and on demand infusions
• Total Factor Consumption. [ Time Frame: 2 years ]
  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.
• Incidence of Less Than Expected Therapeutic Effect (LETE) [ Time Frame: 2 years ]
  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.

Original Secondary Outcome Measures (submitted: April 12, 2011)

• Assessment scores on a 4-point Response Scale for an on-demand bleeding episode, as assessed by subject/caregiver or investigator/qualified staff. The 4 point scale assessments are Excellent, Good, Moderate or No response. [ Time Frame: Up to 2 years ]
• The number of BeneFIX infusions used to treat each bleed. [ Time Frame: Up to 2 years ]
• The number of breakthrough (spontaneous/non-traumatic) bleeds within 48 hours of a prophylaxis dose of BeneFIX . [ Time Frame: Up to 2 years ]
• The average infusion dose and total factor consumption. [ Time Frame: Up to 2 years ]
• The number of subjects with incidences of less-than-expected therapeutic effect (LETE) in the absence of confounding factors. There are 3 circumstances in which LETE can occur. In the on-demand or prophylaxis settings and for low recovery of Factor IX. [ Time Frame: Up to 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B
• Official Title: 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%)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia B

Intervention

• Biological: Nonacog alfa
  Period 1: During on-demand period, dosing at the discretion of investigator.
  Other Name: BeneFIX
• Biological: Nonacog alfa
  Period 2: During the prophylaxis period, 100 IU/kg once weekly
  Other Name: BeneFIX

Study Arms

BeneFIX

Interventions:

• Biological: Nonacog alfa
• Biological: Nonacog alfa

• Publications *: Tortella BJ, Carr ME, Rendo P, Korth-Bradley J, Smith LM, Kavakli K. Once-weekly prophylaxis regimen of nonacog alfa in patients with hemophilia B: an analysis of timing of bleeding event onset. Blood Coagul Fibrinolysis. 2021 Feb 18. doi: 10.1097/MBC.0000000000001012. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 28, 2014): 25
• Original Estimated Enrollment (submitted: April 12, 2011): 24
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Croatia, Korea, Republic of, Malaysia, Mexico, Poland, Singapore, Turkey
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT01335061
• Other Study ID Numbers: B1821010; 3090A1-3306 ( Other Identifier: Alias Study Number ); 2011-000520-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2015