Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Nonacog alfa
Nonacog alfa
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B focused on measuring Hemophilia B, on-demand, prophylaxis, nonacog alfa, BeneFIX, FIX
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.
Sites / Locations
- UMBAL Sveti Georgi, Klinika po hematologia
- The Ottawa Hospital
- University Hospital Center Zagreb
- Eulji University Hospital
- Hospital Tengku Ampuan Afzan
- National Blood Centre
- Hospital y Clinica OCA
- Instituto Biomedico de Investigacion A.C.
- Nzoz Triclinium
- Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
- Singapore General Hospital
- Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bilim Dali
- Hacettepe Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bolumu
- Ege Universitesi Tip Fakultesi
- Gaziantep Universitesi Tip Fakultesi Sahinbey Arastirma ve Uygulama Hastanesi Hematoloji Poliklinigi
- Erciyes Universitesi Tip Fakultesi Hastaneleri M. Kemal Dedeman Onkoloji Hastanesi
- Erciyes Universitesi Tip Fakultesi
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
BeneFIX
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Average Infusion Dose.
The mean dose by per infusion by weight (IU/kg) was reported for both prophylaxis and on demand infusions
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01335061
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%)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
Keywords
Hemophilia B, on-demand, prophylaxis, nonacog alfa, BeneFIX, FIX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BeneFIX
Arm Type
Other
Intervention Type
Biological
Intervention Name(s)
Nonacog alfa
Other Intervention Name(s)
BeneFIX
Intervention Description
Period 1: During on-demand period, dosing at the discretion of investigator.
Intervention Type
Biological
Intervention Name(s)
Nonacog alfa
Other Intervention Name(s)
BeneFIX
Intervention Description
Period 2: During the prophylaxis period, 100 IU/kg once weekly
Primary Outcome Measure Information:
Title
Annualized Number of Bleeding Episodes.
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Response to On-Demand Treatment for All Bleeding Episodes.
Description
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.
Time Frame
2 years
Title
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode.
Description
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.
Time Frame
2 years
Title
Number of Breakthrough (Spontaneous/Non-Traumatic) Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX.
Description
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.
Time Frame
2 years
Title
Average Infusion Dose.
Description
The mean dose by per infusion by weight (IU/kg) was reported for both prophylaxis and on demand infusions
Time Frame
2 years
Title
Total Factor Consumption.
Description
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.
Time Frame
2 years
Title
Incidence of Less Than Expected Therapeutic Effect (LETE)
Description
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.
Time Frame
2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
UMBAL Sveti Georgi, Klinika po hematologia
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
University Hospital Center Zagreb
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Eulji University Hospital
City
Daejeon
ZIP/Postal Code
302-799
Country
Korea, Republic of
Facility Name
Hospital Tengku Ampuan Afzan
City
Kuantan
State/Province
Pahang
ZIP/Postal Code
25200
Country
Malaysia
Facility Name
National Blood Centre
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
Hospital y Clinica OCA
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64000
Country
Mexico
Facility Name
Instituto Biomedico de Investigacion A.C.
City
Aguascalientes
ZIP/Postal Code
20127
Country
Mexico
Facility Name
Nzoz Triclinium
City
Warszawa
ZIP/Postal Code
02-797
Country
Poland
Facility Name
Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bilim Dali
City
Fatih
State/Province
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Hacettepe Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bolumu
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi
City
Bornova/Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Gaziantep Universitesi Tip Fakultesi Sahinbey Arastirma ve Uygulama Hastanesi Hematoloji Poliklinigi
City
Gaziantep
ZIP/Postal Code
27300
Country
Turkey
Facility Name
Erciyes Universitesi Tip Fakultesi Hastaneleri M. Kemal Dedeman Onkoloji Hastanesi
City
KAYSERİ, Erciyes
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Erciyes Universitesi Tip Fakultesi
City
Kayseri
ZIP/Postal Code
38039
Country
Turkey
12. IPD Sharing Statement
Citations:
PubMed Identifier
33631774
Citation
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 Apr 1;32(3):180-185. doi: 10.1097/MBC.0000000000001012.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1821010&StudyName=Study%20To%20Compare%20On-Demand%20Treatment%20To%20A%20Prophylaxis%20Regimen%20Of%20BeneFIX%20In%20Subjects%20With%20Moderately%20Severe%20to%20Severe%20Hemophilia%20B
Description
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Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B
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