Brief Title
Dose-Response Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
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
Brief Summary
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.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Initial Recovery
Secondary Outcome
Area Under the Curve/Dose
Condition
Hemophilia A
Intervention
Antihemophilic factor, recombinant, manufactured protein-free
Study Arms / Comparison Groups
Low Dose
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
38
Start Date
February 2, 2006
Completion Date
April 1, 2007
Primary Completion Date
April 1, 2007
Eligibility Criteria
Inclusion Criteria:
- 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
informed consent.
Exclusion Criteria:
- The subject has a known hypersensitivity to mouse or hamster proteins or to factor
VIII concentrates.
- 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
screening.
- 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
enrollment.
- 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.
Gender
All
Ages
12 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00289536
Organization ID
060403
Responsible Party
Sponsor
Study Sponsor
Baxalta now part of Shire
Study Sponsor
Study Director, Study Director, Takeda
Verification Date
May 2021