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PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Hemophilia A

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ClinicalTrials.gov Identifier: NCT02492984
Recruitment Status : Completed
First Posted : July 9, 2015
Results First Posted : April 4, 2017
Last Update Posted : April 4, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: Intravenous infusions of Xyntha Phase 4

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%).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Intervention Model: Single Group Assignment
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 Xyntha (Moroctocog-alfa (Af-cc), Recombinant Fviii) In Subjects With Hemophilia A In Usual Care Settings In China
Study Start Date : April 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : August 2016


Arm Intervention/treatment
Experimental: Intravenous infusions of Xyntha
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.
Drug: Intravenous infusions of Xyntha
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.
Other Name: Xyntha (Moroctocog-alfa (AF-CC)




Primary Outcome Measures :
  1. Percentage of Participants With Factor VIII (FVIII) Inhibitors [ 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). ]
    Percentage of participants with the product medically important event (MIE) (FVIII inhibitor development during the study).


Secondary Outcome Measures :
  1. Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ 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). ]
    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.

  2. Response Assessment of On-Demand Treatment of Bleeds [ Time Frame: From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. ]
    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.

  3. Number of Infusions Needed to Treat Each New Bleed for On-Demand Treatment [ Time Frame: From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. ]
    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).

  4. Frequency of Xyntha Infusions to Treat Each New Bleed for On-Demand Group [ Time Frame: From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. ]
    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.

  5. Hemostatic Efficacy for Surgical Prophylaxis Treatment [ 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) ]
    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.

  6. Actual Estimated Blood Loss for Surgical Prophylaxis Treatment [ 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) ]
    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.

  7. Number of Participants With Transfusion Requirement for Surgical Prophylaxis Treatment [ 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) ]
    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.

  8. Average Infusion Dose and Total Factor VIII Consumption for On-Demand Treatment and Surgical Prophylaxis Treatment [ 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. ]
    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).

  9. Percentage of Less Than Expected Therapeutic Effect (LETE) in the On-Demand Setting [ Time Frame: From Day 1 up to participants had received treatment for 6 months or participants had achieved 50 EDs whichever occurred first. ]
    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.

  10. Number of Confirmed LETE in the Low Recovery Setting [ Time Frame: From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. ]
    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.



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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 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.

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): NCT02492984


Locations
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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, Jiangsu
Department of Hematology,The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
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, 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
Beijing Children's hospital
Beijing, China, 100045
The second affiliated hospital of chongqing medical university
Chongqing, China, 400010
Children's Hospital of Chongqing Medical University
Chongqing, China, 400014
Hematology Department, Nanfang Hospital, Southern Medical University
Guang Zhou, China, 510515
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine/Hematology Department
Shanghai, China, 200025
Department of Hematology/Children's Hospital of Shanghai
Shanghai, China, 200040
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: NCT02492984     History of Changes
Other Study ID Numbers: B1831083
2015-005040-33 ( EudraCT Number )
First Posted: July 9, 2015    Key Record Dates
Results First Posted: April 4, 2017
Last Update Posted: April 4, 2017
Last Verified: February 2017

Keywords provided by Pfizer:
FVIII inhibitor

Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants