Study Evaluating The Efficacy And Safety Of Xyntha In Children Less Than 6 Years Of Age

Study Overview
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Brief Summary
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This study will be investigating the safety and efficacy of Xyntha (moroctocog alfa (AF-CC)) in male patients less than 6 years old. Annualized bleeding rates and physician / caregiver assessments of responses to treatment will be characterized. FVIII inhibitor levels will be assessed throughout the study.

Detailed Description
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The study was terminated on 22 Sept 2009 due to competition with another Wyeth study for a similar patient population. The decision to terminate the trial was not based on any safety issues.

Official Title
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An Open-Label Study To Evaluate The Efficacy And Safety Of Xyntha In Children Less Than 6 Years Of Age In Usual Care Settings

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Moroctocog alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients less than 6 years of age with moderately severe to severe hemophilia A (FVIII less than or equal to 2%). Treatment history of less than 50 exposure days to prior recombinant or plasma-derived FVIII replacement products. Not receiving treatment for HIV or hepatitis infection, or the patient is on a stable antiviral regimen at the time of enrollment in the study. Exclusion Criteria: Presence of any bleeding disorder in addition to hemophilia A. Inhibitor titer of greater than or equal to 5 Bethesda Units (BU) at screening. Treated with immunomodulatory therapy during the screening period Treatment history of more than 5 exposure days (ED) to Xyntha. Known hypersensitivity to hamster protein.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Other: open label<br> | Biological: Moroctocog alfa<br>* Patients will receive Moroctocog alfa according to their investigator's prescription.<br>|

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) Inhibitor Development | Incidence of inhibitor development was defined as any result determined positive at a central laboratory (Bethesda inhibitor titer of >=0.6 BU/mL) using Nijmegen modification of the Bethesda assay. | Baseline to 24 months or early withdrawal. | 
| Percentage of Participants With Less Than Expected Therapeutic Effects (LETE) in the On-Demand Setting | LETE in the on-demand setting was based on the response to the treatment of a bleeding episode. LETE in the on-demand setting occurred if the participant recorded 2 successive No Response ratings (indicated there was no improvement at all between infusions or during the 24 hour interval following an infusion, or condition worsened) after 2 successive Xyntha infusions, respectively. The infusions was to be administered within 24 hours (=<24 hours) of each other for the treatment of the same bleeding event in the absence of confounding factor. | Baseline to 24 months or early withdrawal. | 
| Percentage of Participants With LETE in the Prophylaxis Setting | The LETE in the prophylaxis setting was the occurrence of a bleed. LETE in the prophylaxis setting occurred if there was a spontaneous bleed within 48 hours (=<48 hours) after a regularly scheduled prophylactic dose of Xyntha (which was not used to treat a bleed) in the absence of confounding factors. | Baseline to 24 months or early withdrawal. | 
| Percentage of Participants With Low Recovery LETE | The LETE could be considered lower than expected recovery of FVIII in the opinion of the investigator following infusion of Xyntha in the absence of confounding factors. | Baseline to 24 months or early withdrawal. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Annualized Bleed Rate (ABR) | An annualized bleeding rate (ABR) for each participant was calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the electronic Infusion Log Diary), divided by his total therapy duration (in days), and then multiplied by 365.25. | Baseline to 24 months or early withdrawal. | 
| Number of Xyntha Infusions Needed to Treat Each New Bleed | The data from the electronic Infusion Log Diary plus the Test Article case report form (CRF) was used to determine the number of infusions administered to treat a bleed. This was calculated by adding the initial 'for a new bleed' (on demand) infusion to any subsequent (on demand) infusions for the (same) 'previously treated bleed'. An on-demand infusion for a 'previously treated bleed' was counted toward the bleed with the most recent start time prior to that infusion. | Baseline to 24 months or early withdrawal. | 
| Response to First On-demand Xyntha Treatment for All New Bleeds as Assessed by the Caregiver | A 4-point response scale to be completed is as defined as follows: (Excellent: definite pain relief/improvement in signs of bleeding starting within 8 hrs after an infusion, with no additional infusion; Good: definite pain relief/improvement in signs of bleeding starting within 8 hrs or following the infusion; Moderate: probable/slight improvement starting after 8 hours following the infusion; No Response: no improvement at all between infusions). | Baseline to 24 months or early withdrawal | 
| Mean Number of Breakthrough (Spontaneous/Non-traumatic) Bleeds | The number of breakthrough (spontaneous/non-traumatic) bleeds within 48 hours following a prophylaxis dose of Xyntha was summarized. The data from the electronic Infusion Log Diary plus the Test Article CRF was used to determine the number of infusions administered to treat a new bleed, counting only those infusions administered =<48 hours after an infusion marked as 'prophylaxis' (which had no associated bleed). | Baseline to 24 months or early withdrawal. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemophilia A, Xyntha, ReFacto, moroctocog alfa, bleeding disorder