Study Evaluating On-Demand Treatment Of Xyntha In Chinese Subjects

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of on-demand treatment with Xyntha in Chinese hemophilia A subjects.

Official Title
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An Evaluation Of The Safety And Efficacy Of On-Demand Treatment With Xyntha (B Domain Deleted Recombinant Factor VIII, Albumin Free) In Chinese Subjects With Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Xyntha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects equal or more than 6 years of age with mild, moderate or severe hemophilia A (FVIII activity: more than 5%, 1-5%, or less than 1%, respectively) Subjects with previous exposure to FVIII replacement therapy If human immunodeficiency virus (HIV) positive, documented cluster of differentiation (CD4) count more than 200/µL within 6 months of study entry Exclusion Criteria: Diagnosed with any bleeding disorder in addition to hemophilia A Current FVIII inhibitor or history of FVIII inhibitor (defined as positive result of the reporting laboratory) Subject has no history of exposure to FVIII products (previously untreated patient [PUP]) Subject is currently utilizing primary FVIII 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 (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] >5 x upper limit of normal [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

Ages Eligible for Study
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Minimum Age: 6 Years

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: Xyntha<br>This trial was an open-label and included assessments of safety, clinical efficacy, and Factor VIII (FVIII) recovery in Chinese subjects with hemophilia A. Subjects received on-demand treatments with Xyntha over a 6-month (calendar day) period. | Biological: Xyntha<br>* Xyntha for on-demand treatment of bleeding episodes were according to investigator prescription during the 6 months observation period. The recovery assessed by determining the Factor VIII (FVIII) concentration (FVIII:C) levels in individual subjects at the initial and final visits. The dose of Xyntha for recovery assessments is: single 50 IU/kg (±5 IU/kg) IV bolus infusion. All Xyntha administrations occurred in the clinic (hospital).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator Hemostatic Efficacy Assessment 8 Hours Post Infusion | The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). | 8 hours post infusion | 
| Investigator Hemostatic Efficacy Assessment 24 Hours Post Infusion | The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). | 24 hours post infusion | 
| Number of Participants With Factor VIII (FVIII) Inhibitor Development | Incidence of FVIII inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory. Incidence was stratified by participant exposure history: Minimally Treated Patients (MTPs): those who had received at least 1 prior FVIII 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. | Day 1 and Month 6 or Early Termination Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FVIII Recovery : Change From Baseline in FVIII Concentration | FVIII recovery was assessed by evaluating the change in FVIII concentration at 6 months compared to baseline. | Day 1 and Month 6 or Early Termination Visit | 
| Number of Participants With Less Than Expected Therapeutic Effect (LETE) | The incidence of LETE, defined for on-demand treatment as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors. | 24 hours after each of 2 successive infusion, up to 6 months | 
| Number of Participants With Thrombosis Allergic-Type Reactions |  | Baseline up to 6 months | 
| Number of Participants With Thrombosis |  | Baseline up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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On-demand treatment; Hemostatic Efficacy Assessments; Factor VIII recovery; Factor VIII Inhibitor; Chinese