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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Procedure: Laboratory Tests

Detailed Description

Regulatory Commitment

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes
• Germany
  • Bremen, Germany, 28177
    • Klinikum Bremen-Mitte gGmbH, Professor Hess Kinderklinik
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule, Hannover
• Italy
  • Firenze, Italy, 50134
    • Agenzia per L'emofilia e Centro Regionale Riferimento Coagulopatie Congenite
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46009
    • Hospital Universitario La Fe
• Turkey
  • Adana, Turkey, 01330
    • Cukurova Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege Universitesi Tip Fakultesi
• Ukraine
  • Lviv, Ukraine, 79044
    • Derzhavna ustanova "Instytut patolohii krovi ta transfuziinoi medytsyny Natsionalnoi akademii

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; The investigator treats subjects with ReFacto AF in the usual care setting.	Procedure: Laboratory Tests; 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).; Other Names: ReFacto AF

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2010
• Primary Completion (Actual): November 24, 2016
• Study Completion (Actual): November 24, 2016

Study Registration Dates

• First Submitted: July 29, 2009
• First Submitted That Met QC Criteria: July 30, 2009
• First Posted (Estimate): July 31, 2009

Study Record Updates

• Last Update Posted (Actual): July 19, 2019
• Last Update Submitted That Met QC Criteria: May 10, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: antibodies; factor VIII; ReFacto AF; inhibitors
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 3082B2-4434; B1831006 (Other Identifier: Alias Study Number); 2008-008436-93 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.