Clinical trial NCT00157157: Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Factor VIII Deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 66
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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:

  1. Platelet count \< 100,000/mm\^3
  2. Hemoglobin concentration \< 10 g/dL (100 g/L)
  3. Serum creatinine \> 1.5 times the upper limit of normal (ULN) for age
  4. 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
* The subject has received any blood product, including packed red blood cells (RBC), platelets, plasma, or cryoprecipitate

Primary outcomes:
measure: Factor VIII Inhibitor Development
timeFrame: Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first)
Secondary outcomes:
measure: Bleeding Episodes Treated With 1 to ≥4 Infusions
timeFrame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
measure: Assessment of Hemostasis for Treatment of Bleeding Episodes
timeFrame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
measure: Annualized Rate of Bleeding Episodes
timeFrame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
measure: Weekly rAHF-PFM Utilization
timeFrame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)
measure: In Vivo Incremental Recovery
timeFrame: 30 minutes pre-infusion to 30 minutes post-infusion
measure: Assessment of Intra-operative Hemostasis
timeFrame: Assessed at the time of discharge from recovery room
measure: Assessment of Postoperative Hemostasis
timeFrame: Assessed at the time of discharge from hospital or clinic
measure: Assessment of Blood Loss During Surgical Procedures
timeFrame: Predicted volumes preoperatively estimated and actual volumes intraoperatively recorded
measure: Adverse Events Deemed Related to Treatment
timeFrame: Reported during the study period which was to be at least 75 exposure days or 3 years (whichever came first)
measure: Development of Antibodies to Heterologous Proteins
timeFrame: Assessed at baseline, throughout the duration of the study, which was to be at least 75 exposure days or 3 years (whichever came first), and at the termination visit.
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: New Orleans
country: United States
state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Vienna
country: Austria
city: Toronto
country: Canada
state: Ontario
city: Caen
country: France
city: Le Kremlin-Bicêtre
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Bremen
country: Germany
city: Frankfurt
country: Germany
city: Hannover
country: Germany
city: Münster
country: Germany
city: Milano
country: Italy
city: San Juan
country: Puerto Rico
city: Barcelona
country: Spain
city: Stockholm
country: Sweden
city: Cardiff
country: United Kingdom
state: Wales
city: London
country: United Kingdom
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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 treatment. J Thromb Haemost. 2007; 5(Suppl 2)v: P-S-180.
citation: Shapiro 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.
citation: Auerswald 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.