Dose-Response Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A - Full Text View

Sponsor:	Baxter Healthcare Corporation
Information provided by:	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00289536

Purpose

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.

Condition	Intervention	Phase
Hemophilia A	Drug: Antihemophilic factor, recombinant, manufactured protein-free	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Crossover Assignment, Pharmacokinetics Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia

MedlinePlus related topics: Hemophilia

Drug Information available for: Octocog alfa Moroctocog Alfa Factor VIII

U.S. FDA Resources

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:

Initial recovery (per-cent increase in IU/dL per IU/kg infused at 30 minutes post-infusion) [ Time Frame: 30 minutes post-infusion ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	January 2006
Study Completion Date:	June 2008

Arms	Assigned Interventions
1: Active Comparator Dose of 15 IU/kg	Drug: Antihemophilic factor, recombinant, manufactured protein-free The enrolled subjects will receive 3 infusions of ADVATE rAHF PFM at doses of 15, 30, and 50 IU/kg in a randomized order for the pharmacokinetic evaluation. The duration between pharmacokinetic infusions will be at least 3 days and not more than 30 days.
2: Active Comparator Dose of 30 IU/kg	Drug: Antihemophilic factor, recombinant, manufactured protein-free The enrolled subjects will receive 3 infusions of ADVATE rAHF PFM at doses of 15, 30, and 50 IU/kg in a randomized order for the pharmacokinetic evaluation. The duration between pharmacokinetic infusions will be at least 3 days and not more than 30 days.
3: Active Comparator Dose of 50 IU/kg	Drug: Antihemophilic factor, recombinant, manufactured protein-free The enrolled subjects will receive 3 infusions of ADVATE rAHF PFM at doses of 15, 30, and 50 IU/kg in a randomized order for the pharmacokinetic evaluation. The duration between pharmacokinetic infusions will be at least 3 days and not more than 30 days.

Eligibility

Ages Eligible for Study:	12 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 5 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00289536

Locations

United States, Arkansas
Arkansas Children´s Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Los Angeles Orthopaedic Hospital
Los Angeles, California, United States, 90007
United States, Illinois
Comprehensive Bleeding Disorders Center
Peoria, Illinois, United States, 61614
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, New Jersey
University of Medicine & Dentistry of NJ, Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, Ohio
Cinicinnati Children´s Hospital Medical Center, Hemophilia Treatment Center
Cincinnati, Ohio, United States, 45229
United States, Oklahoma
University of Oklahoma HSC, Division of Pediatric Hematology/Oncology
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
University of Texas Health Sciences Center, Gulf States Hemophilia & Thrombophilia Center, HMC
Houston, Texas, United States, 77030

Sponsors and Collaborators

Baxter Healthcare Corporation

Investigators

Principal Investigator:	Deborah Brown, MD	The University of Texas Health Science Center, Houston
Principal Investigator:	Ralph Gruppo, MD	Cincinnati Children´s Hospital Medical Center
Principal Investigator:	Michael Tarantino, MD	Comprehensive Bleeding Disorders Center
Principal Investigator:	Jorge Di Paola, MD	University of Iowa
Principal Investigator:	Claire Philipp, MD	University of Medicine & Dentistry of NJ, Robert Wood Johnson Medical School
Principal Investigator:	Kapil Saxena, MD	University of Oklahoma HSC
Principal Investigator:	Doris V Quon, MD	Los Angeles Orthopaedic Hospital
Principal Investigator:	Kimo Stine, MD	Arkansas Children´s Hospital

More Information

No publications provided

Responsible Party:	Baxter Healthcare Corporation ( Jorge Escobar, Clinical Project Manager )
Study ID Numbers:	060403
Study First Received:	February 9, 2006
Last Updated:	July 24, 2008
ClinicalTrials.gov Identifier:	NCT00289536 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Hemorrhagic Disorders
Blood Coagulation Disorders, Inherited
Coagulants
Genetic Diseases, Inborn
Coagulation Protein Disorders
Hematologic Diseases

Therapeutic Uses
Blood Coagulation Disorders
Hematologic Agents
Hemophilia A
Pharmacologic Actions
Factor VIII

ClinicalTrials.gov processed this record on November 27, 2009