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

NCT00289536 | Completed Phase 4 Results DMC

• 1 other identifier: 060403
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 8

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Initial Recovery

  Percent increase in factor VIII concentration per dose from pre- to post-infusion

  Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion

Secondary Outcomes (11)

• Area Under the Curve/Dose

  Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

• Terminal Half-life

  Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

• Area Under the Curve

  Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

• Total Area Under the Curve

  Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

• Total Area Under the Moment Curve

  Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Study Arms (3)

Low Dose

EXPERIMENTAL

Biological: Antihemophilic factor, recombinant, manufactured protein-free

Medium Dose

EXPERIMENTAL

Biological: Antihemophilic factor, recombinant, manufactured protein-free

High Dose

EXPERIMENTAL

Biological: Antihemophilic factor, recombinant, manufactured protein-free

Interventions

Antihemophilic factor, recombinant, manufactured protein-free BIOLOGICAL

15 IU/kg rAHF-PFM

Low Dose

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (8)

Unknown Facility

Little Rock, Arkansas, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Peoria, Illinois, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

New Brunswick, New Jersey, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, United States

Location

Unknown Facility

Houston, Texas, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2006
• First Posted: February 10, 2006
• Study Start: February 2, 2006
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: June 10, 2021
• Results First Posted: January 13, 2011

Record last verified: 2021-05

Locations

US (8)