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Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China

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ClinicalTrials.gov Identifier: NCT02336178
Recruitment Status : Completed
First Posted : January 12, 2015
Results First Posted : May 4, 2017
Last Update Posted : May 4, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
HEMOPHILIA B Drug: Benefix Phase 4

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%).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Benefix
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.
Drug: Benefix

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 Measures :
  1. Percentage of Participants Who Developed Factor IX Inhibitor [ Time Frame: Up to 6 months ]
    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.

  2. Number of Participants With Allergic Reactions [ Time Frame: Up to 6 months ]
    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.

  3. Number of Participants With Thrombotic Events [ Time Frame: Up to 6 months ]
    Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.


Secondary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment) ]
    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.

  2. Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  3. Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  4. Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  5. Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  6. Number of BeneFIX Infusions to Treat Each New Bleed [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  7. Average Infusion Dose and Total Factor IX Consumption in On-demand Setting [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  8. Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  9. Average Infusion Dose and Total Factor IX Consumption in Recovery Setting [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  10. Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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.

  11. Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting [ Time Frame: Up to 6 months or 50 exposure days whichever occurred first ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02336178


Locations
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China, Guangdong
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China, 510515
China, Guizhou
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China, 550004
China, Henan
Henan Provincial People's Hospital
Zhengzhou, Henan, China, 450003
China, Hubei
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China, 430030
China, Hunan
Xiangya Hospital of Centre-South University
Changsha, Hunan, China, 410008
China, Jiangsu
Department of Hematology,The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
Department of Hematology,The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China, 221006
China, Jiangxi
Department of Hematology,Jiangxi Provincial People's Hospital
Nanchang, Jiangxi, China, 330006
China, Shandong
Blood Center of Shandong Province
Jinan, Shandong, China, 250014
China, Shanghai
Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine/Hematology Department
Shanghai, Shanghai, China, 200025
China, Shanxi
Shanxi Medical University Second Hospital
Taiyuan, Shanxi, China, 030001
China, Sichuan
Chengdu Women's and Children's Central Hospital
Chengdu, Sichuan, China, 610073
China, Tianjin
Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)
Tianjin, Tianjin, China, 300020
China, Yunnan
Department of Hematology,The First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, China, 650032
China
Hematology Department,Beijing Children's Hospital, Capital Medical University
Beijing, China, 100045
Children's Hospital of Chongqing Medical University
Chongqing, China, 400014
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02336178     History of Changes
Other Study ID Numbers: B1821052
2016-000765-22 ( EudraCT Number )
First Posted: January 12, 2015    Key Record Dates
Results First Posted: May 4, 2017
Last Update Posted: May 4, 2017
Last Verified: March 2017

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