Dose-Response Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
Information source: Baxalta US Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hemophilia A
Intervention: Antihemophilic factor, recombinant, manufactured protein-free (Biological); Antihemophilic factor, recombinant, manufactured protein-free (Biological); Antihemophilic factor, recombinant, manufactured protein-free (Biological)
Phase: Phase 4
Sponsored by: Baxalta US Inc.
Official(s) and/or principal investigator(s):
Deborah Brown, MD, Principal Investigator, Affiliation: The University of Texas Health Science Center, Houston
Ralph Gruppo, MD, Principal Investigator, Affiliation: Cincinnati Children´s Hospital Medical Center
Michael Tarantino, MD, Principal Investigator, Affiliation: Comprehensive Bleeding Disorders Center
Jorge Di Paola, MD, Principal Investigator, Affiliation: University of Iowa
Claire Philipp, MD, Principal Investigator, Affiliation: University of Medicine & Dentistry of NJ, Robert Wood Johnson Medical School
Kapil Saxena, MD, Principal Investigator, Affiliation: University of Oklahoma HSC
Doris V Quon, MD, Principal Investigator, Affiliation: Los Angeles Orthopaedic Hospital
Kimo Stine, MD, Principal Investigator, Affiliation: Arkansas Children´s Hospital
The purpose of this study is to determine the effect of 3 doses of ADVATE rAHF-PFM on
initial recovery (% increase [IU/dL] per IU/kg infused) and major single-infusion
pharmacokinetic parameters. The 3 doses are 15, 30, and 50 IU/kg. Prior to each infusion,
subjects will not have received treatment with a factor VIII concentrate for at least 3
days. Blood samples will be drawn within 30 minutes pre-infusion and at 0. 25, 0. 5, 1, 3, 6,
9, 24, 28, 32 and 48 hours post-infusion. A washout period of at least 3 days, but no more
than 30 days between the last blood draw and the next infusion will be observed. During
participation, subjects will maintain their preexisting treatment regimens with ADVATE
rAHF-PFM or other factor VIII concentrate.
A secondary objective is to investigate the relationship between pharmacokinetic parameters
at each dose level and the levels of von Willebrand factor ristocetin cofactor activity and
von Willebrand factor antigen at baseline.
Official title: Advate Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (ADVATE rAHF-PFM): A Phase 4 Study to Determine the Pharmacokinetic Response of Patients Diagnosed With Severe Hemophilia A to Different Doses of ADVATE rAHF-PFM
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Initial Recovery
Area Under the Curve/Dose
Area Under the Curve
Total Area Under the Curve
Total Area Under the Moment Curve
Mean Residence Time
Volume of Distribution at Steady State
Maximum Plasma Concentration
Pre-infusion Von Willebrand Factor Ristocetin Cofactor Activity (VWF:Rco)
Pre-infusion Von Willebrand Factor Antigen (VWF:Ag)
Minimum age: 12 Years.
Maximum age: 65 Years.
- The subject has severe hemophilia A as defined by a baseline factor VIII activity <1%
of normal; tested at screening. (A minimum washout period of 3 days is required
before the blood sample can be drawn to determine baseline factor VIII levels.)
- The subject has a documented history of at least 150 exposure days to factor VIII
concentrates (either plasma-derived or recombinant).
- The subject is within 12 to 65 years of age.
- The subject has a Karnofsky performance score >60.
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with CD4 count
>=400 cells/mm3 (CD4 count determined at screening, if necessary).
- The subject or subject´s legally authorized representative has provided written
- The subject has a known hypersensitivity to mouse or hamster proteins or to factor
- The subject has a history of factor VIII inhibitors with titer >=0. 8 BU (Bethesda
Assay) or >=0. 4 BU (Nijmegen modification of the Bethesda Assay) any time prior to
- The subject has a detectable factor VIII inhibitor at screening, >=0. 4 BU (Nijmegen
modification of the Bethesda Assay), in the Baxter central laboratory.
- The subject has severe chronic liver disease as evidenced by, but not limited to, any
of the following: International Normalized Ratio (INR) >1. 4, hypoalbuminemia, portal
vein hypertension including presence of otherwise unexplained splenomegaly and
history of esophageal varices.
- The subject has been diagnosed with an inherited or acquired hemostatic defect other
than hemophilia A (e. g. qualitative platelet defect or von Willebrand´s Disease).
- The subject has participated in another investigational study within 30 days of
- The subject´s clinical condition may require a major or moderate surgery (estimated
blood loss >500 mL) during the period of participation in the study.
Locations and Contacts
Little Rock, Arkansas, United States
Los Angeles, California, United States
Peoria, Illinois, United States
Iowa City, Iowa, United States
New Brunswick, New Jersey, United States
Cincinnati, Ohio, United States
Oklahoma City, Oklahoma, United States
Houston, Texas, United States
Starting date: February 2006
Last updated: June 26, 2015