Study Evaluating On-Demand Treatment With BeneFIX In Chinese Subjects
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Benefix
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B focused on measuring On-demand treatment, Hemostatic efficacy, Factor IX activity, Factor IX recovery, Factor IX inhibitor, Chinese
Eligibility Criteria
Inclusion Criteria:
- Subjects equal or more than 6 years of age with mild, moderate or severe hemophilia B (FIX activity: more than 5%, 1-5%, or less than 1%, respectively)
- Subjects with previous exposure to FIX replacement therapy
- If HIV positive, documented CD4 count more than 200/µL within 6 months of study entry
Exclusion Criteria:
- Diagnosed with any bleeding disorder in addition to hemophilia B
- Current FIX inhibitor or history of FIX inhibitor (defined as >ULN of the reporting laboratory)
- Subject has no history of exposure to FIX products (previously untreated patient [PUP])
- Subject is currently utilizing primary FIX prophylaxis
- Subjects anticipating elective surgery that may be planned to occur in the 6 months following study entry
- Treated with immunomodulatory therapy within 30 days prior to study entry or planned use for the duration of their study participation
- Participated in another investigational drug or device study within 30 days prior to study entry or planned participation for the duration of their study participation
- Subjects with a known hypersensitivity to hamster protein
- Significant hepatic or renal impairment (ALT and AST >5 x ULN, bilirubin >2 mg/dL or serum creatinine >1.25 x ULN)
- Prothrombin Time >1.5 x ULN
- Platelet count <80,000/µL
- Pregnant or breastfeeding women
- Unwilling or unable to follow the terms of the protocol
- Any condition which may compromise the subject's ability to comply with and/or perform study-related activities or that poses a clinical contraindication to study participation, in the opinion of the Investigator or Sponsor
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Benefix
Arm Description
Subjects received on-demand treatments with BeneFIX over a 6-month (calendar day) period.
Outcomes
Primary Outcome Measures
Investigator Hemostatic Efficacy Assessment of Participants After 8 Hours Post Infusion
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.
Investigator Hemostatic Efficacy Assessment of Participants After 24 Hours Post Infusion
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.
Percentage of Participants With FIX Inhibitor Development
Incidence of FIX inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory with Nijmegen assay result >=0.6 Bethesda Unit (BU). Incidence was stratified by participant exposure history - Minimally Treated Patients (MTPs): those who had received at least one prior FIX infusion, and <= 100 documented Exposure Days (EDs); while Previously Treated Patients (PTPs): those who had received >100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, participants were included in the MTP population.
Secondary Outcome Measures
Number of Infusions Required to Treat Each Bleed
The number of BeneFIX infusions required to treat each bleeding episode were analyzed. The average frequency of BeneFIX infusions per hemorrhage incidence to treat every hemorrhage was equal to the total number of injections throughout the study divided by total number of hemorrhagic events.
FIX Incremental Recovery
FIX recovery was assessed by evaluating FIX:C after initial exposure and following 6 months of repeated exposures to BeneFIX. A modified FIX recovery study was performed at Day 1 (Visit 2) and Month 6/Final/Early Termination visits (Visit 4) and when clinically indicated at the applicable on-demand visits. Blood samples for determination of FIX:C were collected immediately before BeneFIX infusion and at 30 minutes (±5 minutes) after the start of infusion. Post-infusion blood samples were collected via venipuncture in arm contralateral to arm used for infusion.
Percentage of Participants With Less Than Expected Therapeutic Effect (LETE)
The incidence of LETE for on-demand treatment was defined as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors.
Percentage of Participants With Allergic-Type Allergic Reactions
Hypersensitivity to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host.
Percentage of Participants With Thrombosis
Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss.
Percentage of Participants With Red Blood Cell (RBC) Agglutination
RBC Agglutination is the clumping of red blood cells in the presence of an antibody. The antibody or other molecule bonded multiple particles and joined them, creating a large complex.
Full Information
NCT ID
NCT00866606
First Posted
March 19, 2009
Last Updated
April 1, 2011
Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00866606
Brief Title
Study Evaluating On-Demand Treatment With BeneFIX In Chinese Subjects
Official Title
An Evaluation Of The Safety And Efficacy Of On-Demand Treatment With BeneFIX (Nonacog Alfa, Recombinant Factor IX) In Chinese Subjects With Hemophilia B
Study Type
Interventional
2. Study Status
Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety and efficacy of on-demand treatment with BeneFIX in Chinese hemophilia B subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
Keywords
On-demand treatment, Hemostatic efficacy, Factor IX activity, Factor IX recovery, Factor IX inhibitor, Chinese
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Benefix
Arm Type
Experimental
Arm Description
Subjects received on-demand treatments with BeneFIX over a 6-month (calendar day) period.
Intervention Type
Biological
Intervention Name(s)
Benefix
Intervention Description
BeneFIX for on-demand treatment of bleeding episodes were according to investigator prescription. FIX recovery was assessed by determining the FIX activity (FIX:C) levels in individual subjects. BeneFIX dosage for recovery assessments: single 75 IU/kg (±5 IU/kg) IV bolus infusion.
Primary Outcome Measure Information:
Title
Investigator Hemostatic Efficacy Assessment of Participants After 8 Hours Post Infusion
Description
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.
Time Frame
8 hours post infusion
Title
Investigator Hemostatic Efficacy Assessment of Participants After 24 Hours Post Infusion
Description
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.
Time Frame
24 hours post infusion
Title
Percentage of Participants With FIX Inhibitor Development
Description
Incidence of FIX inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory with Nijmegen assay result >=0.6 Bethesda Unit (BU). Incidence was stratified by participant exposure history - Minimally Treated Patients (MTPs): those who had received at least one prior FIX infusion, and <= 100 documented Exposure Days (EDs); while Previously Treated Patients (PTPs): those who had received >100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, participants were included in the MTP population.
Time Frame
Baseline up to 6 months
Secondary Outcome Measure Information:
Title
Number of Infusions Required to Treat Each Bleed
Description
The number of BeneFIX infusions required to treat each bleeding episode were analyzed. The average frequency of BeneFIX infusions per hemorrhage incidence to treat every hemorrhage was equal to the total number of injections throughout the study divided by total number of hemorrhagic events.
Time Frame
Baseline up to 6 months
Title
FIX Incremental Recovery
Description
FIX recovery was assessed by evaluating FIX:C after initial exposure and following 6 months of repeated exposures to BeneFIX. A modified FIX recovery study was performed at Day 1 (Visit 2) and Month 6/Final/Early Termination visits (Visit 4) and when clinically indicated at the applicable on-demand visits. Blood samples for determination of FIX:C were collected immediately before BeneFIX infusion and at 30 minutes (±5 minutes) after the start of infusion. Post-infusion blood samples were collected via venipuncture in arm contralateral to arm used for infusion.
Time Frame
Baseline (Visit 2) up to 6 months (Visit 4)
Title
Percentage of Participants With Less Than Expected Therapeutic Effect (LETE)
Description
The incidence of LETE for on-demand treatment was defined as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors.
Time Frame
Baseline up to 6 months
Title
Percentage of Participants With Allergic-Type Allergic Reactions
Description
Hypersensitivity to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host.
Time Frame
Baseline up to 6 months
Title
Percentage of Participants With Thrombosis
Description
Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss.
Time Frame
Baseline up to 6 months
Title
Percentage of Participants With Red Blood Cell (RBC) Agglutination
Description
RBC Agglutination is the clumping of red blood cells in the presence of an antibody. The antibody or other molecule bonded multiple particles and joined them, creating a large complex.
Time Frame
Baseline up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects equal or more than 6 years of age with mild, moderate or severe hemophilia B (FIX activity: more than 5%, 1-5%, or less than 1%, respectively)
Subjects with previous exposure to FIX replacement therapy
If HIV positive, documented CD4 count more than 200/µL within 6 months of study entry
Exclusion Criteria:
Diagnosed with any bleeding disorder in addition to hemophilia B
Current FIX inhibitor or history of FIX inhibitor (defined as >ULN of the reporting laboratory)
Subject has no history of exposure to FIX products (previously untreated patient [PUP])
Subject is currently utilizing primary FIX prophylaxis
Subjects anticipating elective surgery that may be planned to occur in the 6 months following study entry
Treated with immunomodulatory therapy within 30 days prior to study entry or planned use for the duration of their study participation
Participated in another investigational drug or device study within 30 days prior to study entry or planned participation for the duration of their study participation
Subjects with a known hypersensitivity to hamster protein
Significant hepatic or renal impairment (ALT and AST >5 x ULN, bilirubin >2 mg/dL or serum creatinine >1.25 x ULN)
Prothrombin Time >1.5 x ULN
Platelet count <80,000/µL
Pregnant or breastfeeding women
Unwilling or unable to follow the terms of the protocol
Any condition which may compromise the subject's ability to comply with and/or perform study-related activities or that poses a clinical contraindication to study participation, in the opinion of the Investigator or Sponsor
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
Pfizer Investigational Site
City
Guangzhou
State/Province
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
Pfizer Investigational Site
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Pfizer Investigational Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Pfizer Investigational Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Pfizer Investigational Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Pfizer Investigational Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
22776196
Citation
Yang R, Zhao Y, Wang X, Sun J, Jin J, Wu D, Charnigo R, O'Brien A, Zhong Z, Rendo P. Evaluation of the safety and efficacy of recombinant factor IX (nonacog alfa) in minimally treated and previously treated Chinese patients with haemophilia B. Haemophilia. 2012 Sep;18(5):e374-8. doi: 10.1111/j.1365-2516.2012.02907.x. Epub 2012 Jul 9. No abstract available.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3090A1-3305&StudyName=Study%20Evaluating%20On-Demand%20Treatment%20With%20BeneFIX%20In%20Chinese%20Subjects
Description
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Study Evaluating On-Demand Treatment With BeneFIX In Chinese Subjects
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