The study will be investigating safety in patients who switch to ReFacto AF from ReFacto and other Factor VIII products.
The trial was terminated prematurely on 28 March 2013, due to the inability to recruit the planned number of subjects. The decision to terminate the trial was not based on any safety or efficacy concerns and agreement to close the study in March 2013 was agreed with EMA prior to closure activity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
208
Providing moroctocog alfa (AF-CC) as test article for use during this study.
Laboratory samples are collected during study visits, in order to collect safety and efficacy data related to the administration of test article.
Number of Participants With Clinically Significant Factor VIII Inhibitor Development
Number of participants with clinically significant FVIII inhibitor development after switching from ReFacto to moroctocog alfa (AF-CC). Clinically significant inhibitors are defined as a central laboratory confirmed positive inhibitor (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay present at 2 consecutive blood draws within a 6-week interval) and within 28 days before the initial or within 28 days following the second positive FVIII inhibitor sample collection one of the following: the need for the participant to administer alternative hemostatic products in order to achieve sufficient efficacy, or ≥2 adverse event reports of decreased drug effect (or other adverse event indicating a decrease in the efficacy of the test article). The blood sample collection for these results must also be between the date of first dose of study medication and 28 days after the last dose of study medication.
Time frame: 100 exposure days to study medication (approx. 2 years)
Annualized Bleeding Rates (ABRs)
An ABR for each participant will be calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the Infusion Log Diary case report form), divided by his total therapy duration (in days), then multiplied by 365.25.
Time frame: 100 exposure days to study medication (approx. 2 years)
Response Assessment of First On-demand Treatment of New Bleeds
A 4-point scale of assessment of 'on-demand' treatment (administration of an unscheduled bolus infusion of Refacto-AF to stop bleeding) is defined as: * Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered. * Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; or, Definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered. * Moderate: Probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode. * No Response: No improvement at all between infusions or during the 24-hour interval following an infusion, or condition worsens.
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Pfizer Investigational Site
Vienna, Austria
Pfizer Investigational Site
Brussels, Belgium, Belgium
Pfizer Investigational Site
Brussels, Belgium
Pfizer Investigational Site
Leuven, Belgium
Pfizer Investigational Site
Copenhagen, Denmark
Pfizer Investigational Site
Helsinki, Finland
Pfizer Investigational Site
Kuopio, Finland
Pfizer Investigational Site
Chambray-lès-Tours, France
Pfizer Investigational Site
Clermont-Ferrand, France
Pfizer Investigational Site
Le Chesnay, France
...and 64 more locations
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of ReFacto AF Infusions to Treat Each New Bleed
The Infusion Log Diary case report form (CRF) was used to determine the number of test article infusions administered to treat a bleed. This was calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time).
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of Bleeding Episodes Occurring ≤48 Hours After a Prophylaxis Infusion
First, the bleed start time from the Infusion Log Diary CRF was used to determine the number of breakthrough bleeds that occurred ≤48 hours after an infusion marked as "Prophylaxis" (which had no associated bleed). If there was more than 1 bleed location (ie, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. If a response was given, or if a bleed time was given, but "On Demand" was not listed as "treatment type", it was still counted as an on-demand bleed for analyses/summaries. Bleeding episodes were not categorized as spontaneous (atraumatic) or traumatic.
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of Participants With Breakthrough Bleeds
The number of participants with any breakthrough bleed was reported.
Time frame: 100 exposure days to study medication (approx. 2 years)
Total Factor Consumption (TFC) Following a Non-prophylaxis Regimen at Baseline for All Participants
The total amount (in International Units \[IU\]) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Time frame: 100 exposure days to study medication (approx. 2 years)
TFC Following a Prophylaxis Regimen at Baseline for All Participants
The total amount (in IU) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Time frame: 100 exposure days to study medication (approx. 2 years)
Average Infusion Dose
The average infusion dose for each participant was calculated as his total factor consumption (in IU) divided by the number of infusions administered. Summary statistics were reported for both of these variables separately for those participants classified at baseline as following an on-demand regimen, and for those on a primary or secondary prophylaxis regimen.
Time frame: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the On-demand Setting
The calculation of incidence of on-demand LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the On Demand LETE CRF), and the denominator was the number of bleeding episodes treated in an on-demand setting. This denominator could include new bleeding episodes in prophylaxis participants breakthrough bleeds), and if subsequent on-demand doses for such a bleed met the on-demand LETE criteria, then an on-demand LETE was reported.
Time frame: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the Prophylaxis Setting
The calculation of incidence of prophylaxis LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the Prophylactic LETE CRF), and the denominator was the number of routine prophylaxis infusions. Each infusion was classified in the infusion log ("Prophylaxis/ On Demand/ Preventive"), and participants were instructed to select "On Demand" if the infusion was to treat a bleed, even if the participant typically followed a prophylaxis regimen. Only the infusions classified as "Prophylaxis" were counted in this denominator.
Time frame: 100 exposure days to study medication (approx. 2 years)