Study of Safety And Efficacy Of ReFacto AF In Previously Untreated Hemophilia A Patients In The Usual Care Setting

Study Overview
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Brief Summary
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Study to evaluate the safety and effectiveness of ReFacto AF for the treatment of severe hemophilia A in patients who have not yet received treatment for their hemophilia. Study subjects will be males less than 6 years old who have not taken any clotting factor or other blood products before the study. The safety and effectiveness of ReFacto AF will be determined in this study by tests and procedures done at the doctor's office.

Detailed Description
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Regulatory Commitment

Official Title
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AN OPEN-LABEL STUDY OF THE SAFETY AND EFFICACY OF REFACTO AF IN PREVIOUSLY UNTREATED PATIENTS IN USUAL CARE SETTINGS

Conditions
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Hemophilia A

Intervention / Treatment
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* Procedure: Laboratory Tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects <6 years of age with severe hemophilia A (FVIII:C <1%) based on clinical records, including newborns. No prior exposure to factor products or any blood products. Exclusion Criteria: Presence of any bleeding disorder in addition to hemophilia A. Treatment with any investigational agent or device within the past 30 days. Any condition(s) that compromises the ability to collect study-related observations, or that poses a contraindication to study participation (these conditions include, but are not limited to, inadequate medical history to assure study eligibility; and expectation of poor adherence to study requirements).

Ages Eligible for Study
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Maximum Age: 6 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>The investigator treats subjects with ReFacto AF in the usual care setting. | Procedure: Laboratory Tests<br>* Blood draws to determine the level of factor VIII activity before and after dosing at appropriate visits, and blood draws to determine levels of factor VIII inhibitor (antibody to factor VIII).<br>* Other names: ReFacto AF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Developed Clinically Significant Factor VIII (FVIII) Inhibitors During the Course of the Study | Percentage of participants who developed clinically significant FVIII inhibitors: those persistent over a defined period with clinically impactful effects like breakthrough bleed, low recovery, etc., during the course of the study. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Bleeding Rate (ABR) | Annualized bleeding rate was calculated as the number of bleeds divided by the treatment interval duration (enrollment visit to final visit) and then multiplied by 365.25. If there was more than 1 bleed location (like ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. | 2 years | 
| Total Number of Infusions to Treat a New Bleed Classified on Basis of Response to First On-Demand Treatment With Refacto AF | Number of infusions of Refacto AF required to treat a new bleed were classified on basis of the response to at 4-point response scale of assessment (excellent, good, moderate and no response). Assessment was completed each time a participant experienced a new bleed requiring an 'on-demand' IV infusion. Excellent: definite pain relief and/or improvement in bleeding signs within 8 hours (hr) after infusion, no additional infusion administered; Good: definite pain relief and/or improvement in bleeding signs within 8 hr after infusion, at least 1 additional infusion administered for complete resolution or with no additional infusion administered; Moderate: probable or slight improvement starting after 8 hr following infusion, at least 1 additional infusion administered for complete resolution; No Response: no improvement at all between infusions or during 24 hr interval following infusion or condition worsen. Bleeds for which response not recorded, reported as: Data Not Recorded. | 2 years | 
| Total Number of Infusions Needed for Resolution of Bleeding Episodes Classified on Basis of Response to Study Drug Infusion | Number of infusions of Refacto AF required for resolution of a bleeding episodes were classified on basis of the response at 4-point response scale of assessment (excellent, good, moderate and no response). Excellent: definite pain relief and/or improvement in bleeding signs within 8 hours (hr) after infusion, no additional infusion administered; Good: definite pain relief and/or improvement in bleeding signs within 8 hr after infusion, at least 1 additional infusion administered for complete resolution or with no additional infusion administered; Moderate: probable or slight improvement starting after 8 hr following infusion, at least 1 additional infusion administered for complete resolution; No Response: no improvement at all between infusions or during 24 hr interval following infusion or condition worsen. Bleeds for which response not recorded, reported as: Data Not Recorded. | Within 48 hours after infusion, up to 2 years treatment duration | 
| Total Number of Breakthrough Bleeding Episodes Occurring Within 48 Hours After a Prophylaxis Infusion of ReFacto AF | The number of breakthrough bleeds (spontaneous or traumatic) within 48 hours following a prophylaxis dose of ReFacto AF are summarized. If there was more than 1 bleed location (like ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. | 2 years | 
| Consumption of Total International Units of Factor VIII |  | 2 years | 
| Consumption of Total International Units of Factor VIII Per Year | Consumption of total international units of Factor VIII per year was calculated for a participant: dividing the total consumption of factor VIII by participant's treatment interval duration (in days), then multiplying by 365.25. | 2 years | 
| Mean Dose (IU) of Study Drug Consumed Per Infusion | Mean dose for each participant was calculated as participant's total factor VIII consumption (in IU) divided by the number of infusions administered. | 2 years | 
| Consumption of Total International Units of Factor VIII by Weight | Consumption of total international units of Factor VIII by weight was calculated for a participant: dividing the total consumption of factor VIII by participant's weight (the most recently recorded). | 2 years | 
| Consumption of Total International Units of Factor VIII Per Year by Weight | Consumption of total international units of Factor VIII per year by weight was calculated for a participant: the total consumption of factor VIII divided by participant's treatment interval duration (in days), then multiplying by 365.25 and then dividing by participant's weight (the most recently recorded). | 2 years | 
| Mean Dose (IU) of Study Drug Consumed Per Infusion by Weight | Mean dose for each participant was calculated as participant's total factor consumption (in IU) divided by the number of infusions administered and then dividing by participant's weight (the most recently recorded). | 2 years | 
| Mean of Total Number of Infusions of Study Drug Received |  | 2 years | 
| Mean of Total Number of Days Participants Exposed to Study Drug |  | 2 years | 
| Number of Participants Who Required Dose Escalation of Their Prescribed Prophylaxis Regimen During Their Participation in This Study | The number of participants who met the dose escalation criteria were prescribed a higher dose and/or were prescribed more frequent doses. When dose escalation was required, the specific dose and dosing schedule was at the investigator's discretion. | 2 years | 
| Percentage of Bleeding Episodes With Less-Than-Expected Therapeutic Effect (LETE) in On-Demand (OD) Setting | LETE occurs in OD setting if participant recorded 2 successive No Response (no improvement at all between infusions, or condition worsens) ratings after 2 successive infusions of study drug. Infusions must have been given within 24 hours (hr) of each other for treatment of same bleeding event in absence of confounding factors (known presence or subsequent identification of a FVIII inhibitor, known inadequate dose for type and/or severity of bleed in opinion of investigator, delay of greater than (>) 4 hr between onset of bleed to infusion, delay of >24 hr before administration of a follow-up infusion, known compromised study drug, faulty administration of study drug, participant had an underlying, predisposing condition responsible for bleed in opinion of investigator, ongoing trauma responsible for continued bleeding. | 2 years | 
| Percentage of Bleeding Episodes With Less-Than-Expected Therapeutic Effect (LETE) in the Prophylaxis Setting | LETE in prophylaxis setting if there was a spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of study drug (which was not used to treat a bleed) in the absence of confounding factors (known presence or subsequent identification of a FVIII inhibitor, known inadequate prophylactic dose [a dose less than that prescribed in participant's regimen], known lack of adherence to the prescribed prophylaxis regimen, known compromised study drug, faulty administration of study drug, participant had an underlying, predisposing condition responsible for the bleed in the opinion of the investigator, traumatic injury responsible for bleeding. | 2 years | 
| Total Number of Events of Potential Less-Than-Expected Therapeutic Effect (LETE) in the Low Recovery Setting | LETE was lower than expected recovery of FVIII in the opinion of the investigator following infusion of study drug in the absence of confounding factors (known presence or subsequent identification of a FVIII inhibitor, known compromised study drug, faulty administration of study drug including inadequate dosing). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ReFacto AF, factor VIII, inhibitors, antibodies