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

NCT ID: NCT00243386

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-04
• Study Completion Date: 2010-06-16

Brief Summary

The primary purpose of this randomized, two-arm parallel clinical study in 66 previously treated patients with severe or moderately severe hemophilia A is to compare the rate of bleeding episodes for standard prophylaxis (20-40 IU/kg every 48 ± 6 hours; actual dose determined by the investigator) with that of alternate prophylaxis (20-80 IU/kg every 72 + 6 hours; actual dose determined by Baxter utilizing an algorithm and the patient's pharmacokinetic data). The rates of bleeding episodes for the on-demand regimen and the prophylaxis regimens will also be compared for the cross-over portion of the study. Enrolled patients will be treated originally on demand for a period of 6 months and then they will be randomized into one of the prophylaxis arms. Prophylactic treatment will last for a period of 12 months +/- 2 weeks.

Conditions

Hemophilia A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Standard prophylaxis

Group Type: ACTIVE_COMPARATOR

Antihemophilic factor, recombinant, manufactured protein-free

Intervention Type: DRUG

Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator

2

PK-driven prophylaxis

Group Type: EXPERIMENTAL

Antihemophilic factor, recombinant, manufactured protein-free

Intervention Type: DRUG

PK-driven prophylaxis: 20-80 IU/kg every 72+/-6 hours, actual dose determined by Baxter using an algorithm and the patient´s pharmacokinetic data

Interventions

Antihemophilic factor, recombinant, manufactured protein-free

Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator

Intervention Type: DRUG

Antihemophilic factor, recombinant, manufactured protein-free

PK-driven prophylaxis: 20-80 IU/kg every 72+/-6 hours, actual dose determined by Baxter using an algorithm and the patient´s pharmacokinetic data

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as tested at screening
• 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 7 to 65 years of age
• The subject has a Karnofsky performance score > (greater than) 60
• The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4 count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)
• The subject has been on a documented on-demand treatment regimen for at least 12 months immediately prior to enrollment
• The subject has a documented history (e.g. in medical charts or dispensing information, or signed investigator statement) of at least 8 joint hemorrhages in the 12 months immediately prior to enrollment
• The subject resides within the coverage area of the mobile compliance device; coverage area will be determined at screening
• The subject or the subject's legally authorized representative has provided written informed consent

Exclusion Criteria

• The subject has a known hypersensitivity to factor VIII concentrates or mouse or hamster proteins
• The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by Bethesda or Nijmegen assay) at any time prior to screening
• The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 BU (by Nijmegen 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's Disease)
• The subject has been treated during the last sixty (60) days prior to or is being treated at screening/enrollment with an immunomodulating drug.
• The subject has participated in another investigational study within thirty (30) days of enrollment
• The subject has previously participated in a clinical study with rAHF-PFM
• The subject's clinical condition may require a major surgery (defined as moderate to critical risk and perioperative blood loss ≥ 500 mL) during the period of the subject's participation in the study
• The subject is female of childbearing potential with a positive pregnancy test

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Los Angeles, California, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

Minneapolis, Minnesota, United States

New York, New York, United States

Oklahoma City, Oklahoma, United States

Portland, Oregon, United States

Hershey, Pennsylvania, United States

Seattle, Washington, United States

Vienna, , Austria

Brno, , Czechia

Prague, , Czechia

Athens, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Szombathely, , Hungary

Florence, , Italy

Milan, , Italy

Gdansk, , Poland

Krakow, , Poland

Lublin, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Moscow, , Russia

Ljubljana, , Slovenia

Cardiff, , United Kingdom

Nottingham, , United Kingdom

Countries

United States; Austria; Czechia; Greece; Hungary; Italy; Poland; Russia; Slovenia; United Kingdom

References

Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012 Mar;10(3):359-67. doi: 10.1111/j.1538-7836.2011.04611.x.

Reference Type: DERIVED

PMID: 22212248 (View on PubMed)

Other Identifiers

060201

Identifier Type: -

Identifier Source: org_study_id