Study of Safety And Efficacy Of ReFacto AF In Previously Untreated Hemophilia A Patients In The Usual Care Setting
- Conditions
- Hemophilia A
- Interventions
- Procedure: Laboratory Tests
- Registration Number
- NCT00950170
- Lead Sponsor
- Pfizer
- Brief Summary
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
Regulatory Commitment
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 23
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Laboratory Tests The investigator treats subjects with ReFacto AF in the usual care setting.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Developed Clinically Significant Factor VIII (FVIII) Inhibitors During the Course of the Study 2 years 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.
- Secondary Outcome Measures
Name Time Method Total Number of Infusions to Treat a New Bleed Classified on Basis of Response to First On-Demand Treatment With Refacto AF 2 years 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.
Annualized Bleeding Rate (ABR) 2 years 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.
Total Number of Infusions Needed for Resolution of Bleeding Episodes Classified on Basis of Response to Study Drug Infusion Within 48 hours after infusion, up to 2 years treatment duration 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.
Total Number of Breakthrough Bleeding Episodes Occurring Within 48 Hours After a Prophylaxis Infusion of ReFacto AF 2 years 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 2 years Consumption of Total International Units of Factor VIII Per Year 2 years 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 (IU) of Study Drug Consumed Per Infusion by Weight 2 years 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).
Mean of Total Number of Infusions of Study Drug Received 2 years Percentage of Bleeding Episodes With Less-Than-Expected Therapeutic Effect (LETE) in the Prophylaxis Setting 2 years 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.
Mean Dose (IU) of Study Drug Consumed Per Infusion 2 years 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 2 years 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 2 years 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 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 2 years 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.
Percentage of Bleeding Episodes With Less-Than-Expected Therapeutic Effect (LETE) in On-Demand (OD) Setting 2 years 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.
Total Number of Events of Potential Less-Than-Expected Therapeutic Effect (LETE) in the Low Recovery Setting 2 years 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).
Trial Locations
- Locations (11)
Klinikum Bremen-Mitte gGmbH, Professor Hess Kinderklinik
🇩🇪Bremen, Germany
Cukurova Universitesi Tip Fakultesi
🇹🇷Adana, Turkey
CHU de Nantes
🇫🇷Nantes, France
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Medizinische Hochschule, Hannover
🇩🇪Hannover, Niedersachsen, Germany
Agenzia per L'emofilia e Centro Regionale Riferimento Coagulopatie Congenite
🇮🇹Firenze, Italy
Hospital Universitario La Paz
🇪🇸Madrid, Spain
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Istanbul Universitesi Cerrahpasa Tip Fakultesi
🇹🇷Istanbul, Turkey
Derzhavna ustanova "Instytut patolohii krovi ta transfuziinoi medytsyny Natsionalnoi akademii
🇺🇦Lviv, Ukraine
Ege Universitesi Tip Fakultesi
🇹🇷Bornova, Izmir, Turkey