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

Study Overview
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Brief Summary
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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
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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%).

Official Title
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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

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Intravenous infusions of Xyntha


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous infusions of Xyntha<br>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<br>* 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.<br>* Other names: Xyntha (Moroctocog-alfa (AF-CC);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Factor VIII (FVIII) Inhibitors | Percentage of participants with the product medically important event (MIE) (FVIII inhibitor development during the study). | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 
| 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. | From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. | 
| 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). | From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. | 
| 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. | From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. | 
| 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. | 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) | 
| 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. | 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 | 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. | 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) | 
| 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). | 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. | 
| 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. | From Day 1 up to participants had received treatment for 6 months or participants had achieved 50 EDs whichever occurred first. | 
| 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. | From Day 1 up to participants had received treatment for 6 months or when participants had achieved 50 EDs whichever occurred first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FVIII inhibitor