Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection

NCT00952822 | Completed Phase 1 Results DMC

• 1 other identifier: 060702
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to determine the pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve

  Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method

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

Secondary Outcomes (9)

• Total Area Under the Curve

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

• Adjusted in Vivo Incremental Recovery

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

• Terminal Half-life

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

• Weight-Adjusted Clearance

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

• Mean Residence Time

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

Study Arms (2)

1

EXPERIMENTAL

ADVATE reconstituted in 2 mL sterile water for infusion

Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)

2

ACTIVE COMPARATOR

ADVATE reconstituted in 5 mL sterile water for infusion

Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)

Interventions

Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) BIOLOGICAL

Subjects are randomized to receive an infusion of rAHF-PFM reconstituted in 2 mL sterile water for infusion (SWFI) followed (after a wash-out period) by rAHF-PFM reconstituted in 5 mL SWFI or in 5 mL then 2 mL SWFI(cross-over design). Each subject will receive 2 infusions.

Also known as: ADVATE

1; 2

Eligibility Criteria

• Age: 2 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 or subject's legally authorized representative has provided written informed consent
• The subject has severe hemophilia A as defined by a baseline FVIII activity \<= 1% of normal; tested at screening
• The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days
• The subject is \>= 12 to \<= 65 years of age for the complete pharmacokinetic assessment and \>= 2 to \< 12 years for the incremental recovery assessment The subject has a Karnofsky performance score \> 60
• The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count \>= 200 cells/mm³ (CD4 count determined at screening, if necessary)

You may not qualify if:

• The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates
• The subject has a history of FVIII inhibitors with titer \>= 0. 5 BU (Bethesda Assay) or \>= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening
• The subject has a detectable FVIII inhibitor at screening, \>= 0.4 BU (Nijmegen modification of the Bethesda Assay), in the 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 Disease)
• The subject has received another investigational product within 30 days of enrollment
• The subject's clinical condition may require major or moderate surgery (estimated blood loss \> 500 mL) during the period of participation in the study
• Subjects with clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
• The subject is a female of childbearing potential with a positive pregnancy test at screening

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (11)

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Lexington, Kentucky, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

New Brunswick, New Jersey, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 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 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: August 8, 2008
• Primary Completion: October 23, 2009
• Study Completion: October 23, 2009
• Last Updated: May 24, 2021
• Results First Posted: July 21, 2011

Record last verified: 2021-04

Locations

US (11)