Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A

Study Overview
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Brief Summary
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Hemophilia A is an X-linked recessive, congenital bleeding disorder caused by deficient or defective coagulation factor VIII (FVIII). Prophylaxis is recommended as the standard of care for boys with severe haemophilia by WHO and World Federation Of Hemophilia (WFH). The efficacy and safety of prophylaxis in preventing bleeds and arthropathy in patients with hemophilia has been confirmed in well-designed clinical studies.To keep the factor level above 1%, the standard dosage for patients with severe hemophilia A is 20-40 Units /kg/infusion (average 30 Units /kg) every other day or three times a week. This dosage has a very high consumption of factor, up to 5000-6000 international unit (IU)/kg/year. The high consumption of factor and cost present a major barrier to use the standard prophylaxis in many countries particularly in the developing world. In China the majority of boys with severe hemophilia A can only pay for on-demand treatment or low-dose prophylaxis. Ao after the affordability of patients was solved and many patients will get more chance to receive standard prophylaxis. This study is designed to evaluate the Annual Bleeding rate (ABR), joint health outcomes and QoL outcomes in subjects using ADVATE(Recombinant Human Coagulation Factor VIII for injection) standard prophylaxis under the conditions of routine practice.

Official Title
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Evaluate Efficacy and Safety of ADVATE in the Standard Prophylaxis Treatment of Severe or Moderately Severe Hemophilia A.

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Recombinant Human Coagulation Factor VIII for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has hemophilia A with FVIII≤2 %. Previously treated patients (PTPs). Age from 2 to 18 years. Exclusion Criteria: Subject has known hypersensitivity to the active substance or any of the excipients. Subject has known allergic reaction to mouse or hamster proteins. Subject has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving another FVIII concentrate or device during the course of this study. Subject is planned, or likely to have surgery during the study period. Subject has end-stage renal failure or evidence of a severe or uncontrolled systemic disease as judged by the investigator. Subject has full-blown Acquired Immuno Deficiency Syndrome (AIDS),determined by Cluster Determinant 4+(CD4+) and clinical presentation. Subject has active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 5 times the upper limit of normal). Subject has clinical or laboratory evidence of severe liver impairment including (but not limited to) a recent and persistent international normalized ratio (INR)> 1.4, and/or the presence of splenomegaly and/or significant spider angioma on physical exam, and/or a history of esophageal hemorrhage or documented esophageal varices. The subject in the opinion of the investigator is unable or unwilling to comply with study protocol Subject is a family member of the investigator or site staff

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: ADVATE<br>The baseline ABR will be assessed from bleeding log and clinic records from preceding year. Subjects will initially be treated standard prophylaxis(20 - 40 IU/Kg body weight every 48 ± 6 hours) with Recombinant Human Coagulation Factor VIII for injection(ADVATE) for 1 year. Subjects must be prescribed ADVATE by the treating physician. Data will be collected over a period of 2 years from the time of study enrollment. Study visits are to coincide with routinely rescheduled and emergency visits. Available data from these visits shall be transcribed onto the case report forms (CRFs). | Drug: Recombinant Human Coagulation Factor VIII for injection<br>* Subjects will initially be treated standard prophylaxis(20 - 40 IU/Kg body weight 2 times one week) with ADVATE for 1 year.<br>* Other names: ADVATE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ABR | To evaluate the Annual Bleeding rate (ABR) in subjects using standard prophylaxis under the conditions of routine practice. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of new target joints | Incidence of new target joints. | 3 months | 
| Pettersson score of joint | Status of joint health by X-ray using Pettersson score | 3 months | 
| magnetic resonance imaging scoring of joint | Status of joint health by magnetic resonance imaging scoring system. | 6 months | 
| Hemophilia Joint Health Score (HJHS) of joint | Status of joint health using HJHS | 3 months | 
| Number of ADAVTE units | Number of Recombinant Human Coagulation Factor VIII for injection (ADAVTE) units required for bleed cessation and Number of ADVATE infusions required for bleed cessation | 3 months | 
| QoL of patients wiht hemophilia | QoL assessment by Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) | 3 months | 
| Inhibitor rate | Inhibitor rate monitoring: inhibitor will be tested at entry of study, every 3 months and at end of study. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemophilia A, standard prophylaxis, Recombinant Human Coagulation Factor VIII for injection, ADVATE, Pediatric