Back to resultsPF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Hemophilia A
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Intravenous infusions of Xyntha
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A focused on measuring FVIII inhibitor
Eligibility Criteria
Inclusion Criteria:
- Male and/or Female subjects with Hemophilia A.
- Subjects/parents/legal representatives must be able to comply with registry procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc).
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study.
Exclusion Criteria:
- Presence of any other bleeding disorder in addition to hemophilia A.
- Treatment with immunomodulatory therapy (e.g., intravenous immunoglobulin, routine systemic corticosteroids, cyclosporins, anti-TNF agents) within 30 days prior to study entry or planned use for the duration of their study participation.
- Subjects with a past history of, or current factor VIII inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 BU/mL.
- Subjects with known hypersensitivity to the active substance or to any of the excipients of Xyntha.
- Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
- 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 (these conditions include, but are not limited to, inadequate medical history to assure study eligibility; expectation of poor compliance in provision of observations for study-related documentation), in the opinion of the Investigator.
- Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation (exception for studies on Xyntha).
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
Sites / Locations
- 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
- Department of Hematology,The First Affiliated Hospital of Soochow University
- Department of Hematology,Jiangxi Provincial People's Hospital
- Blood Center of Shandong Province
- 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
- Beijing Children's hospital
- The second affiliated hospital of chongqing medical university
- Children's Hospital of Chongqing Medical University
- Hematology Department, Nanfang Hospital, Southern Medical University
- Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine/Hematology Department
- Department of Hematology/Children's Hospital of Shanghai
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intravenous infusions of Xyntha
Arm Description
Enrolled subjects will be treated with intravenous infusions of Xyntha for: • On-Demand treatment, • Surgical Prophylaxis at a dose and frequency prescribed by the subject's treating physician in accordance with the Xyntha label and will be adjusted solely according to medical and therapeutic necessity.
Outcomes
Primary Outcome Measures
Percentage of Participants With Factor VIII (FVIII) Inhibitors
Percentage of participants with the product medically important event (MIE) (FVIII inhibitor development during the study).
Secondary Outcome Measures
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was considered treatment emergent if it started for the first time in a participant on or after the first day of active treatment, or the event started before the first day of active treatment but increased in severity during active treatment. AEs included both SAEs and non-serious AEs.
Response Assessment of On-Demand Treatment of Bleeds
The proportion of infusions (initial and subsequent for a bleed) in each response category (excellent, good, moderate, no response) was reported. Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered. Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least 1 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: Probable or slight improvement starting after 8 hours following the infusion, with at least 1 additional infusion administered for complete resolution of the bleeding episode. No Response: No improvement at all between infusions or during the 24 hour interval following an infusion, or condition worsens.
Number of Infusions Needed to Treat Each New Bleed for On-Demand Treatment
The number of Xyntha infusions administered to treat a bleed was determined. This was calculated by adding the on-demand initial treatment and any on-demand follow-up infusions for the same bleed (same bleed start date/time).
Frequency of Xyntha Infusions to Treat Each New Bleed for On-Demand Group
The number of bleeds resolved with 1, 2, 3, 4, or >4 infusions was reported for each of the categories (1, 2, 3, 4, or >4 infusions needed to treat the bleed), in which the numerator was the number of bleeds falling into each category, and the denominator was the total number of new bleeds across all participants.
Hemostatic Efficacy for Surgical Prophylaxis Treatment
Assessment of hemostatic efficacy was determined by the investigator and/or surgeon using the 4 point Surgical Hemostasis Efficacy Rating Scale. Excellent: Achieved hemostasis comparable to that expected after similar surgery in a non hemophilic participant. Good: Prolonged time to hemostasis, with somewhat increased bleeding compared to that expected after similar surgery in a non hemophilic participant. Moderate: Obviously delayed hemostasis, but manageable with additional infusions. No Response: No hemostatic response. The percentage of observations in each hemostatic efficacy response category (excellent, good, moderate, none) was reported.
Actual Estimated Blood Loss for Surgical Prophylaxis Treatment
Number of participants with blood loss in each category (Abnormal, Normal, and Absence). Blood loss during the intraoperative and the postoperative period were assessed by investigator or surgeon, which were rated as Abnormal, Normal, and Absence. Abnormal blood loss meant the blood loss was higher over the expectation for the non hemophilic participant.
Number of Participants With Transfusion Requirement for Surgical Prophylaxis Treatment
Number of participants with transfusion requirement for surgical prophylaxis treatment. Transfusion requirements during the intraoperative and the postoperative period were assessed by investigator or surgeon. The number of units and types of blood products transfused were recorded if applicable.
Average Infusion Dose and Total Factor VIII Consumption for On-Demand Treatment and Surgical Prophylaxis Treatment
The total amount (IU) infused for each Xyntha infusion recorded in the study drug infusion log case report form (CRF) was summed to calculate the total factor VIII consumption for each participant. The average infusion dose for each participant was calculated as his total factor VIII consumption (in IU) divided by the number of infusions administered. The total factor VIII consumption, divided by number of infusions, was summarized similarly to average infusion dose (IU).
Percentage of Less Than Expected Therapeutic Effect (LETE) in the On-Demand Setting
LETE occurred in the on-demand setting if 2 successive "No Response" ratings were recorded after 2 successive Xyntha drug infusions, respectively.The infusions must have been administered within 24 hours (less than or equal to 24 hours) of each other for treatment of the same bleeding event in the absence of confounding factors (prespecified). Therefore, LETE in the on-demand setting was based on the response to treatment of a bleeding episode (including those occurring during the surgical prophylaxis period). Note that on-demand treatments administered during the surgical prophylaxis period were also to be included.
Number of Confirmed LETE in the Low Recovery Setting
LETE could also be lower than expected recovery of FVIII in the opinion of the investigator following infusion of Xyntha in the absence of confounding factors. The only confounding factors for low recovery were: known presence or subsequent identification of a FVIII inhibitor; known compromised Xyntha; faulty administration of Xyntha, including inadequate dosing.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02492984
Brief Title
PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Hemophilia A
Official Title
An Open-label, Single-arm, Post- Authorization Pragmatic Clinical Trial On The Safety And Efficacy Of Xyntha (Moroctocog-alfa (Af-cc), Recombinant Fviii) In Subjects With Hemophilia A In Usual Care Settings In China
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
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
An open-label, single-arm, post- authorization pragmatic clinical trial on the safety and efficacy of Xyntha (Moroctocog-alfa (AF-CC), Recombinant FVIII) in subjects with hemophilia A in usual care settings in China for approximately 6 months or or approximately 50 exposure days whichever occurs first
Detailed Description
The purpose of this post-approval study is to provide supplementary information relating to the use of Xyntha (Moroctocog-alfa (AF-CC), Recombinant FVIII) in Chinese subjects with hemophilia A, especially on the safety and efficacy in different populations of Chinese hemophilia A 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 (FVIII:C <1%).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
FVIII inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
85 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous infusions of Xyntha
Arm Type
Experimental
Arm Description
Enrolled subjects will be treated with intravenous infusions of Xyntha for: • On-Demand treatment, • Surgical Prophylaxis at a dose and frequency prescribed by the subject's treating physician in accordance with the Xyntha label and will be adjusted solely according to medical and therapeutic necessity.
Intervention Type
Drug
Intervention Name(s)
Intravenous infusions of Xyntha
Other Intervention Name(s)
Xyntha (Moroctocog-alfa (AF-CC)
Intervention Description
Enrolled subjects will be treated with intravenous infusions of Xyntha for: • On-Demand treatment, • Surgical Prophylaxis at a dose and frequency prescribed by the subject's treating physician in accordance with the Xyntha label and will be adjusted solely according to medical and therapeutic necessity.
Primary Outcome Measure Information:
Title
Percentage of Participants With Factor VIII (FVIII) Inhibitors
Description
Percentage of participants with the product medically important event (MIE) (FVIII inhibitor development during the study).
Time Frame
From Day 1 up to 28 calendar days after End of Treatment (participants had received treatment for 6 months or when participants had achieved 50 exposure days [EDs] whichever occurred first).
Secondary Outcome Measure Information:
Title
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was considered treatment emergent if it started for the first time in a participant on or after the first day of active treatment, or the event started before the first day of active treatment but increased in severity during active treatment. AEs included both SAEs and non-serious AEs.
Time Frame
From Day 1 up to 28 calendar days after End of Treatment (participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first).
Title
Response Assessment of On-Demand Treatment of Bleeds
Description
The proportion of infusions (initial and subsequent for a bleed) in each response category (excellent, good, moderate, no response) was reported. Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered. Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least 1 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: Probable or slight improvement starting after 8 hours following the infusion, with at least 1 additional infusion administered for complete resolution of the bleeding episode. No Response: No improvement at all between infusions or during the 24 hour interval following an infusion, or condition worsens.
Time Frame
From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first.
Title
Number of Infusions Needed to Treat Each New Bleed for On-Demand Treatment
Description
The number of Xyntha infusions administered to treat a bleed was determined. This was calculated by adding the on-demand initial treatment and any on-demand follow-up infusions for the same bleed (same bleed start date/time).
Time Frame
From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first.
Title
Frequency of Xyntha Infusions to Treat Each New Bleed for On-Demand Group
Description
The number of bleeds resolved with 1, 2, 3, 4, or >4 infusions was reported for each of the categories (1, 2, 3, 4, or >4 infusions needed to treat the bleed), in which the numerator was the number of bleeds falling into each category, and the denominator was the total number of new bleeds across all participants.
Time Frame
From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first.
Title
Hemostatic Efficacy for Surgical Prophylaxis Treatment
Description
Assessment of hemostatic efficacy was determined by the investigator and/or surgeon using the 4 point Surgical Hemostasis Efficacy Rating Scale. Excellent: Achieved hemostasis comparable to that expected after similar surgery in a non hemophilic participant. Good: Prolonged time to hemostasis, with somewhat increased bleeding compared to that expected after similar surgery in a non hemophilic participant. Moderate: Obviously delayed hemostasis, but manageable with additional infusions. No Response: No hemostatic response. The percentage of observations in each hemostatic efficacy response category (excellent, good, moderate, none) was reported.
Time Frame
From day of surgery to postoperative period (at least 1-3 days post operation or until adequate wound healing for minor surgery or 4-6 days post operation or until threat resolved or adequate wound healing for major surgery)
Title
Actual Estimated Blood Loss for Surgical Prophylaxis Treatment
Description
Number of participants with blood loss in each category (Abnormal, Normal, and Absence). Blood loss during the intraoperative and the postoperative period were assessed by investigator or surgeon, which were rated as Abnormal, Normal, and Absence. Abnormal blood loss meant the blood loss was higher over the expectation for the non hemophilic participant.
Time Frame
From day of surgery to postoperative period (at least 1-3 days post operation or until adequate wound healing for minor surgery or 4-6 days post operation or until threat resolved or adequate wound healing for major surgery)
Title
Number of Participants With Transfusion Requirement for Surgical Prophylaxis Treatment
Description
Number of participants with transfusion requirement for surgical prophylaxis treatment. Transfusion requirements during the intraoperative and the postoperative period were assessed by investigator or surgeon. The number of units and types of blood products transfused were recorded if applicable.
Time Frame
From day of surgery to postoperative period (at least 1-3 days post operation or until adequate wound healing for minor surgery or 4-6 days post operation or until threat resolved or adequate wound healing for major surgery)
Title
Average Infusion Dose and Total Factor VIII Consumption for On-Demand Treatment and Surgical Prophylaxis Treatment
Description
The total amount (IU) infused for each Xyntha infusion recorded in the study drug infusion log case report form (CRF) was summed to calculate the total factor VIII consumption for each participant. The average infusion dose for each participant was calculated as his total factor VIII consumption (in IU) divided by the number of infusions administered. The total factor VIII consumption, divided by number of infusions, was summarized similarly to average infusion dose (IU).
Time Frame
On-Demand Group: Day 1 up to 6 months or 50 EDs whichever occurred first. Surgical Prophylaxis Group: Day of surgery to postoperative period. The duration of postoperative period is specified in previous endpoints.
Title
Percentage of Less Than Expected Therapeutic Effect (LETE) in the On-Demand Setting
Description
LETE occurred in the on-demand setting if 2 successive "No Response" ratings were recorded after 2 successive Xyntha drug infusions, respectively.The infusions must have been administered within 24 hours (less than or equal to 24 hours) of each other for treatment of the same bleeding event in the absence of confounding factors (prespecified). Therefore, LETE in the on-demand setting was based on the response to treatment of a bleeding episode (including those occurring during the surgical prophylaxis period). Note that on-demand treatments administered during the surgical prophylaxis period were also to be included.
Time Frame
From Day 1 up to participants had received treatment for 6 months or participants had achieved 50 EDs whichever occurred first.
Title
Number of Confirmed LETE in the Low Recovery Setting
Description
LETE could also be lower than expected recovery of FVIII in the opinion of the investigator following infusion of Xyntha in the absence of confounding factors. The only confounding factors for low recovery were: known presence or subsequent identification of a FVIII inhibitor; known compromised Xyntha; faulty administration of Xyntha, including inadequate dosing.
Time Frame
From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first.
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and/or Female subjects with Hemophilia A.
Subjects/parents/legal representatives must be able to comply with registry procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc).
Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study.
Exclusion Criteria:
Presence of any other bleeding disorder in addition to hemophilia A.
Treatment with immunomodulatory therapy (e.g., intravenous immunoglobulin, routine systemic corticosteroids, cyclosporins, anti-TNF agents) within 30 days prior to study entry or planned use for the duration of their study participation.
Subjects with a past history of, or current factor VIII inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 BU/mL.
Subjects with known hypersensitivity to the active substance or to any of the excipients of Xyntha.
Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
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 (these conditions include, but are not limited to, inadequate medical history to assure study eligibility; expectation of poor compliance in provision of observations for study-related documentation), in the opinion of the Investigator.
Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation (exception for studies on Xyntha).
Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
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
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
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,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
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
Beijing Children's hospital
City
Beijing
ZIP/Postal Code
100045
Country
China
Facility Name
The second affiliated hospital of chongqing medical university
City
Chongqing
ZIP/Postal Code
400010
Country
China
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
ZIP/Postal Code
400014
Country
China
Facility Name
Hematology Department, Nanfang Hospital, Southern Medical University
City
Guang Zhou
ZIP/Postal Code
510515
Country
China
Facility Name
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine/Hematology Department
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Department of Hematology/Children's Hospital of Shanghai
City
Shanghai
ZIP/Postal Code
200040
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
33269010
Citation
Yang R, Zhao Y, Wang X, Sun J, Wu R, Jin C, Jin J, Wu D, Rendo P, Sun F, Rupon J, Huard F, Korth-Bradley JM, Xu L, Luo B, Liu YC. Safety and Efficacy of Moroctocog Alfa (AF-CC) in Chinese Patients with Hemophilia A: Results of Two Open-Label Studies. J Blood Med. 2020 Nov 25;11:439-448. doi: 10.2147/JBM.S241605. eCollection 2020.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com
Description
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PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Hemophilia A
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