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

NCT00243386 | Completed Phase 4 Results DMC

• 1 other identifier: 060201
• Study Type: interventional
• Target: 82
• Locations: 10 countries
• Sites: 29

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

Outcome Measures

Primary Outcomes (2)

• Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens

  Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Study Part 2): 1. Standard prophylaxis (20-40 IU/kg (every 48 ±6 hour), exact regimen determined by investigator) 2. PK-driven prophylaxis (20-80 IU/kg (every 72 ±6 hour), exact regimen determined by sponsor) Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X = bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the t-test.

  12 months ±2 weeks

• Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens

  Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.

  12 months ±2 weeks

Secondary Outcomes (26)

• Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens

  On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)

• Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens

  On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)

• Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens

  On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)

• Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm

  12 months ±2 weeks

• Bleeding Episodes Treated With 1 to ≥4 Infusions

  Throughout the study period (4 years and 5 months)

Study Arms (2)

1

ACTIVE COMPARATOR

Standard prophylaxis

Drug: Antihemophilic factor, recombinant, manufactured protein-free

2

EXPERIMENTAL

PK-driven prophylaxis

Drug: Antihemophilic factor, recombinant, manufactured protein-free

Interventions

Antihemophilic factor, recombinant, manufactured protein-free DRUG

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

1

Eligibility Criteria

• Age: 7 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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (29)

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Los Angeles, California, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Minneapolis, Minnesota, United States

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New York, New York, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Hershey, Pennsylvania, United States

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Seattle, Washington, United States

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Vienna, Austria

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Brno, Czechia

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Prague, Czechia

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Athens, Greece

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Budapest, Hungary

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Debrecen, Hungary

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Pécs, Hungary

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Szeged, Hungary

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Szombathely, Hungary

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Florence, Italy

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Milan, Italy

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Gdansk, Poland

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Krakow, Poland

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Lublin, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Moscow, Russia

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Ljubljana, Slovenia

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Cardiff, United Kingdom

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Nottingham, United Kingdom

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Related Publications (1)

• 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.

  PMID: 22212248 DERIVED

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2005
• First Posted: October 24, 2005
• Study Start: January 4, 2006
• Primary Completion: June 16, 2010
• Study Completion: June 16, 2010
• Last Updated: May 19, 2021
• Results First Posted: November 20, 2012

Record last verified: 2021-04

Locations

SL (1); IT (2); US (9); PL (5); GB (2); GR (1); AU (1); HU (5); RU (1); CZ (2)