Clinical trial NCT00289536: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2006-02-10
Enrollment: 38
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Initial Recovery
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
Secondary outcomes:
measure: Area Under the Curve/Dose
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Terminal Half-life
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Area Under the Curve
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Total Area Under the Curve
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Total Area Under the Moment Curve
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Weight-adjusted Clearance
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Mean Residence Time
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Volume of Distribution at Steady State
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Pre-infusion Von Willebrand Factor Ristocetin Cofactor Activity (VWF:Rco)
timeFrame: At baseline and before each pharmacokinetic evaluation
measure: Pre-infusion Von Willebrand Factor Antigen (VWF:Ag)
timeFrame: At baseline and before each pharmacokinetic evaluation
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Peoria
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: New Brunswick
country: United States
state: New Jersey
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: