Back to resultsSafety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China
Primary Purpose
HEMOPHILIA B
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Benefix
Sponsored by
About this trial
This is an interventional treatment trial for HEMOPHILIA B
Eligibility Criteria
Inclusion Criteria:
- Male and/or female subjects with hemophilia B.
- Subjects/parents/legal representatives must be able to comply with study procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc)
Exclusion Criteria:
- Presence of any other bleeding disorder in addition to hemophilia B. Subjects with a past history of, or current factor IX inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 Bethesda Unit (BU)/mL.
- Subjects with known hypersensitivity to the active substance or to any of the excipients of BeneFIX.
- Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
Sites / Locations
- Nanfang Hospital, Southern Medical University
- The Affiliated Hospital of Guizhou Medical University
- Henan Provincial People's Hospital
- Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
- Xiangya Hospital of Centre-South University
- Department of Hematology,The First Affiliated Hospital of Soochow University
- Department of Hematology,The Affiliated Hospital of Xuzhou Medical University
- Department of Hematology,Jiangxi Provincial People's Hospital
- Blood Center of Shandong Province
- Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine/Hematology Department
- Shanxi Medical University Second Hospital
- Chengdu Women's and Children's Central Hospital
- Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)
- Department of Hematology,The First Affiliated Hospital of Kunming Medical University
- Hematology Department,Beijing Children's Hospital, Capital Medical University
- Children's Hospital of Chongqing Medical University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Benefix
Arm Description
This is a single arm study. Subjects will be treated with Benefix by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Developed Factor IX Inhibitor
Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.
Number of Participants With Allergic Reactions
FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.
Number of Participants With Thrombotic Events
Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.
Secondary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period
For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >=14 days.
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX
The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred <=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period
For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >= 14 days.
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response
Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.
Number of BeneFIX Infusions to Treat Each New Bleed
The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. 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 and Total Factor IX Consumption in On-demand Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting
Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive "no response" ratings recorded after 2 successive BeneFIX drug infusions, respectively.
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting
Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02336178
Brief Title
Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China
Official Title
An Open-label, Single-arm, Post-authorization Pragmatic Clinical Trial On The Safety And Efficacy Of Benefix (Nonacog Alfa, Recombinant Factor Ix) In Subjects With Hemophilia B In Usual Care Settings In China
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
August 2016 (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 post-approval study is to evaluate the safety and efficacy of Benefix in subjects with hemophilia B in usual care settings in China.
Detailed Description
The purpose of this post-approval study is to provide supplementary information relating to the use of BeneFIX in Chinese subjects with hemophilia B, especially on the safety and efficacy in different populations of Chinese hemophilia B patients, in particular in pediatric patients <6 years of age, pediatric patients ≥6 to ≤12 years of age, Previously Untreated Patients (PUPs) , subjects receiving prophylaxis treatment after enrollment in the study, and severe patients (FIX activity <1%).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HEMOPHILIA B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Masking
None (Open Label)
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Benefix
Arm Type
Experimental
Arm Description
This is a single arm study. Subjects will be treated with Benefix by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert.
Intervention Type
Drug
Intervention Name(s)
Benefix
Intervention Description
Subjects will be treated by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert.
The treatment duration is approximately 6 months (±7 days) or approximately 50 Exposure Days (EDs) (±5 EDs) (see protocol definition on EDs) whichever occurs first.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Developed Factor IX Inhibitor
Description
Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.
Time Frame
Up to 6 months
Title
Number of Participants With Allergic Reactions
Description
FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.
Time Frame
Up to 6 months
Title
Number of Participants With Thrombotic Events
Description
Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Time Frame
Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment)
Title
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period
Description
For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >=14 days.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX
Description
The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred <=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period
Description
For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >= 14 days.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response
Description
Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Number of BeneFIX Infusions to Treat Each New Bleed
Description
The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. 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
Up to 6 months or 50 exposure days whichever occurred first
Title
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting
Description
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting
Description
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting
Description
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting
Description
Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive "no response" ratings recorded after 2 successive BeneFIX drug infusions, respectively.
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
Title
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting
Description
Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).
Time Frame
Up to 6 months or 50 exposure days whichever occurred first
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and/or female subjects with hemophilia B.
Subjects/parents/legal representatives must be able to comply with study procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc)
Exclusion Criteria:
Presence of any other bleeding disorder in addition to hemophilia B. Subjects with a past history of, or current factor IX inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 Bethesda Unit (BU)/mL.
Subjects with known hypersensitivity to the active substance or to any of the excipients of BeneFIX.
Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
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
Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Facility Name
The Affiliated Hospital of Guizhou Medical University
City
Guiyang
State/Province
Guizhou
ZIP/Postal Code
550004
Country
China
Facility Name
Henan Provincial People's Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Facility Name
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
Xiangya Hospital of Centre-South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410008
Country
China
Facility Name
Department of Hematology,The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Department of Hematology,The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221006
Country
China
Facility Name
Department of Hematology,Jiangxi Provincial People's Hospital
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Name
Blood Center of Shandong Province
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250014
Country
China
Facility Name
Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine/Hematology Department
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Shanxi Medical University Second Hospital
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030001
Country
China
Facility Name
Chengdu Women's and Children's Central Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610073
Country
China
Facility Name
Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Department of Hematology,The First Affiliated Hospital of Kunming Medical University
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650032
Country
China
Facility Name
Hematology Department,Beijing Children's Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100045
Country
China
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
ZIP/Postal Code
400014
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
34032739
Citation
Yang R, Wu R, Sun J, Sun F, Rupon J, Huard F, Korth-Bradley JM, Xu L, Luo B, Liu YC, Rendo P. First open-label, single-arm, prospective study of real-world use of FIX replacement therapy in a predominantly pediatric hemophilia B population in China. Medicine (Baltimore). 2021 May 28;100(21):e26077. doi: 10.1097/MD.0000000000026077.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1821052&StudyName=Safety%20and%20Efficacy%20of%20Benefix%20%28nonacog%20Alfa%2C%20Recombinant%20%20Factor%20Ix%29%20in%20Patients%20with%20Hemophilia%20B%20in%20Usual%20Care%20Settings%20in%20
Description
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Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China
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