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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

Status: Completed

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.

Clinical Details

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

Secondary outcome:

Area Under the Curve/Dose

Terminal Half-life

Area Under the Curve

Total Area Under the Curve

Total Area Under the Moment Curve

Weight-adjusted Clearance

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. Gender(s): Both.


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


- 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

Additional Information

Starting date: February 2006
Last updated: June 26, 2015

Page last updated: August 23, 2015

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