Trial Outcomes & Findings for Study of Safety And Efficacy Of ReFacto AF In Previously Untreated Hemophilia A Patients In The Usual Care Setting (NCT NCT00950170)

A total of 23 participants were enrolled in this non-randomized open-label study \& they received ReFacto albumin free (AF) at dose \& frequency prescribed by each participant's treating physician as per local standard of care \& in accordance with summary of product characteristics (SmPC). Participants were expected to be in study for about 26 months

The study was conducted at 11 centers across various countries. Participants less than 6 years of age with severe hemophilia A (FVIII activity in plasma \[FVIII:C\]\<1%) who had not received any prior factor products or blood products for their hemophilia A were enrolled in this study.

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

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.

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.

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.

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.

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.

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.

Mean dose for each participant was calculated as participant's total factor VIII consumption (in IU) divided by the number of infusions administered.

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).

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).

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).

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.

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.

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.

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).