Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients
Recombinant Antihemophilic Factor Manufactured and Formulated Without Added Human or Animal Proteins (rAHF-PFM): Evaluation of Immunogenicity, Efficacy, and Safety in Previously Untreated Patients With Hemophilia A
2 other identifiers
interventional
66
10 countries
35
Brief Summary
The purpose of this study is to evaluate whether Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) is effective and safe in the treatment of hemophilia A patients who have not been treated with factor VIII (FVIII) before.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Apr 2004
Longer than P75 for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2004
CompletedFirst Submitted
Initial submission to the registry
September 9, 2005
CompletedFirst Posted
Study publicly available on registry
September 12, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
September 11, 2009
CompletedResults Posted
Study results publicly available
July 15, 2011
CompletedMay 24, 2021
April 1, 2021
5.4 years
September 9, 2005
February 15, 2011
April 28, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Factor VIII Inhibitor Development
Percentage of treated participants who developed factor VIII inhibitors
Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first)
Secondary Outcomes (10)
Bleeding Episodes Treated With 1 to ≥4 Infusions
Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
Assessment of Hemostasis for Treatment of Bleeding Episodes
Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
Annualized Rate of Bleeding Episodes
Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
Weekly rAHF-PFM Utilization
Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
In Vivo Incremental Recovery
30 minutes pre-infusion to 30 minutes post-infusion
- +5 more secondary outcomes
Study Arms (1)
Single Arm - All Participants
EXPERIMENTALAll subjects enrolled in the study who meet the eligibility criteria.
Interventions
Treatment regimens were determined by the investigator, and may have been any combination of standard prophylaxis (25 to 50 IU/kg body weight, 3 to 4 times per week), investigator-determined prophylaxis, and/or on-demand treatment (dose selected by investigator). The treatment of bleeding episodes and perioperative management was at the discretion of the investigator and consistent with the institution's standard of care. For incremental recovery assessments, a single infusion at 50 +/- 5 IU/kg was to be given. Immune tolerance induction (ITI) therapy for subjects who developed factor VIII inhibitors was at the discretion of the investigator, based on the institution's guidelines or described in peer-reviewed literature, and was to be approved by the sponsor's medical director. rAHF-PFM was to be administered intravenously via bolus infusion, except for perioperative management when it may have been given either by continuous or bolus infusion.
Eligibility Criteria
You may qualify if:
- The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level \<= 2% of normal, as documented at screening
- The subject is \< 6 years of age
- The subject's legally authorized representative has provided written informed consent
You may not qualify if:
- The subject has a history of exposure to factor VIII other than rAHF PFM or more than 3 infusions of commercially available rAHF PFM (i.e., ADVATE) within 28 days prior to screening, as determined by the subject's medical history. Any infusion of factor VIII replacement products prior to the 28-day period excludes the subject from participation
- The subject has received more than 3 infusions of rAHF PFM (commercially available and/or study product) between screening and prior to the initial recovery infusion
- The subject has a detectable inhibitor to factor VIII, as measured in the screening sample by the Nijmegen assay in the central laboratory
- The subject has a history of inhibitor to factor VIII at any time prior to screening
- The subject has a known hypersensitivity to rAHF PFM
- The subject has any 1 of the following laboratory abnormalities at the time of screening:
- Platelet count \< 100,000/mm\^3
- Hemoglobin concentration \< 10 g/dL (100 g/L)
- Serum creatinine \> 1.5 times the upper limit of normal (ULN) for age
- Total bilirubin \> 2 times the ULN for age
- The subject has an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's disease)
- The subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), as determined by the subject's medical history
- At the time of enrollment, the subject has a clinically significant chronic disease other than hemophilia A
- The subject is currently participating in another investigational drug study, or has participated in any clinical study involving an investigational drug within 120 days of the screening visit
- The subject (or the subject's legally authorized representative) is identified by the investigator as being unable or unwilling to cooperate with study procedures
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Unknown Facility
Phoenix, Arizona, United States
Unknown Facility
Little Rock, Arkansas, United States
Unknown Facility
Los Angeles, California, United States
Unknown Facility
Washington D.C., District of Columbia, United States
Unknown Facility
Atlanta, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Peoria, Illinois, United States
Unknown Facility
Indianapolis, Indiana, United States
Unknown Facility
Iowa City, Iowa, United States
Unknown Facility
New Orleans, Louisiana, United States
Unknown Facility
Ann Arbor, Michigan, United States
Unknown Facility
Detroit, Michigan, United States
Unknown Facility
Minneapolis, Minnesota, United States
Unknown Facility
New Hyde Park, New York, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Philadelphia, Pennsylvania, United States
Unknown Facility
Houston, Texas, United States
Unknown Facility
Vienna, Austria
Unknown Facility
Toronto, Ontario, Canada
Unknown Facility
Caen, France
Unknown Facility
Le Kremlin-Bicêtre, France
Unknown Facility
Lyon, France
Unknown Facility
Marseille, France
Unknown Facility
Nantes, France
Unknown Facility
Paris, France
Unknown Facility
Bremen, Germany
Unknown Facility
Frankfurt, Germany
Unknown Facility
Hanover, Germany
Unknown Facility
Münster, Germany
Unknown Facility
Milan, Italy
Unknown Facility
San Juan, Puerto Rico
Unknown Facility
Barcelona, Spain
Unknown Facility
Stockholm, Sweden
Unknown Facility
Cardiff, Wales, United Kingdom
Unknown Facility
London, United Kingdom
Related Publications (4)
Ewenstein B., Patrone L, Schroth P, Spotts G, Fritsch S, Pavlova B, Ehrlich H. Efficacy of antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) in bleed prevention. J Thromb Haemost. 2007; 5(Suppl 2): P-S-179.
RESULTEwenstein B., Patrone L, Schroth P, Spotts G, Fritsch S, Pavlova B, Ehrlich H. Efficacy of antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) in bleed treatment. J Thromb Haemost. 2007; 5(Suppl 2)v: P-S-180.
RESULTShapiro A, Gruppo R, Pabinger I, Collins PW, Hay CR, Schroth P, Casey K, Patrone L, Ehrlich H, Ewenstein BM. Integrated analysis of safety and efficacy of a plasma- and albumin-free recombinant factor VIII (rAHF-PFM) from six clinical studies in patients with hemophilia A. Expert Opin Biol Ther. 2009 Mar;9(3):273-83. doi: 10.1517/14712590902729392.
PMID: 19216617RESULTAuerswald G, Thompson AA, Recht M, Brown D, Liesner R, Guzman-Becerra N, Dyck-Jones J, Ewenstein B, Abbuehl B. Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A. Thromb Haemost. 2012 Jun;107(6):1072-82. doi: 10.1160/TH11-09-0642. Epub 2012 Apr 4.
PMID: 22476554DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2005
First Posted
September 12, 2005
Study Start
April 1, 2004
Primary Completion
September 11, 2009
Study Completion
September 11, 2009
Last Updated
May 24, 2021
Results First Posted
July 15, 2011
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.