Pharmacokinetic Study of ADVATE 3000 IU in Previously Treated Patients With Severe Hemophilia A

NCT00916032 | Completed Phase 4 Results DMC

• 2 other identifiers: 0608012008-007347-13
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 4

Brief Summary

The objective of this clinical study is to compare the pharmacokinetic parameters of 3000 IU Advate using one 3000 IU potency vial dissolved in 5 mL diluent with that of 3000 IU Advate using two vials of 1500 IU potency dissolved in 5 mL diluent each (administered in 10 mL diluent in total) in previously treated patients with severe hemophilia A (factor VIII level \< 1%).

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). Chromogenic Assay

  Computed using the linear trapezoidal method.

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.

• Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). One-stage Activated Partial Thromboplastin Time (aPTT) Assay

  Computed using the linear trapezoidal method.

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.

Secondary Outcomes (16)

• Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). Chromogenic Assay

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.

• Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). One-stage aPTT Assay

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.

• Incremental Recovery at Cmax - Chromogenic Assay

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3 hours.

• Incremental Recovery at Cmax - One-stage aPTT Assay

  Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3 hours.

• Incremental Recovery at 30 Minutes- Chromogenic Assay

  30 minutes pre-infusion and 30 minutes post-infusion

Study Arms (2)

1

ACTIVE COMPARATOR

One infusion using a 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent followed by a second infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total)

Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]

2

ACTIVE COMPARATOR

One infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total) followed by a second infusion of one 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent

Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]

Interventions

Octocog alfa (recombinant human coagulation factor VIII) [ADVATE] BIOLOGICAL

Participants will receive 3000 IU Advate using one 3000 IU potency vial dissolved in 5 mL diluent followed by two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total) or the alternate sequence

Also known as: ADVATE, Antihemophilic Factor (Recombinant)- Plasma/albumin free method (rAHF-PFM)

1; 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is 18 to 65 years old, at the time of screening
• Participant has provided signed informed consent
• Participant has severe hemophilia A, defined by a baseline FVIII level \< 1% of normal, as tested at screening at the central laboratory
• Participant's weight is between 55-65 kg
• Participant was previously treated with FVIII concentrate(s) for a minimum of 150 exposure days prior to study entry
• If Participant is HIV positive, he must be immunocompetent as determined with a CD4 count ≥ 200 cells/mm³ (CD4 count at screening)
• Participant is willing and able to comply with the requirements of the protocol

You may not qualify if:

• Participant has a detectable FVIII inhibitor at screening, with a titer ≥ 0.4 Bethesda unit (BU) (Nijmegen modification of the Bethesda Assay) measured at the central laboratory
• Participant has a history of FVIII inhibitors with a titer ≥ 0.4 BU (by Nijmegen assay) or ≥ 0.5 BU (by Bethesda Assay) at any time prior to screening
• Participant has undergone a surgery within 21 days prior to screening or within 6 weeks prior to the anticipated first pharmacokinetics(PK) infusion
• Participant has an abnormal renal function (serum creatinine \> 1.5 mg/dL)
• Participant has active hepatic disease (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \>5 times the upper limit of normal)
• Participant 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
• Participant has clinical and/or laboratory evidence of abnormal hemostasis from causes other than hemophilia A (eg, late-stage chronic liver disease, immune thrombocytopenia purpura)
• Participant is currently receiving, or is scheduled to receive during the course of the clinical study, an immunomodulating drug other than anti-retroviral chemotherapy (eg, alfa-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day)
• Participant has a known hypersensitivity to mouse or hamster proteins
• Participant has participated in another clinical study involving an investigational product or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this clinical study
• Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures
• Participant is a member of the team conducting this clinical study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, or parents) as well as employees of the investigator or site personnel conducting the clinical study.

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (4)

Unknown Facility

Sofia, 1233, Bulgaria

Location

Unknown Facility

Kirov, Russia

Location

Unknown Facility

Moscow, 125167, Russia

Location

Unknown Facility

Saint Petersburg, 195213, Russia

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

F8 protein, human; 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: June 5, 2009
• First Posted: June 8, 2009
• Study Start: June 29, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: May 19, 2021
• Results First Posted: September 5, 2013

Record last verified: 2021-04

Locations

BU (1); RU (3)