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Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00157157
First received: September 9, 2005
Last updated: February 25, 2013
Last verified: February 2013
History of Changes
  Purpose

The purpose of this study is to evaluate whether Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) is effective and safe in the treatment of hemophilia A patients who have not been treated with factor VIII (FVIII) before.


Condition Intervention Phase
Hemophilia A
 Biological: Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recombinant Antihemophilic Factor Manufactured and Formulated Without Added Human or Animal Proteins (rAHF-PFM): Evaluation of Immunogenicity, Efficacy, and Safety in Previously Untreated Patients With Hemophilia A

Resource links provided by NLM:

MedlinePlus related topics: Hemophilia
U.S. FDA Resources

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Factor VIII Inhibitor Development [ Time Frame: Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: Yes ]
    Percentage of treated participants who developed factor VIII inhibitors


Secondary Outcome Measures:
  • Bleeding Episodes Treated With 1 to ≥4 Infusions [ Time Frame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: No ]
    The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis

  • Assessment of Hemostasis for Treatment of Bleeding Episodes [ Time Frame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: No ]

    Number of rAHF-PFM-treated bleeding episodes with treater assessment of hemostasis (4-point ordinal scale):

    Excellent: Full pain relief & bleeding cessation within ~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis;

    Good: Definite pain relief and/or improvement in bleeding within ~8 hrs after infusion. Possibly requires >1 infusion for complete resolution;

    Fair: Probable or slight relief of pain & slight improvement in bleeding within ~8 hrs after infusion. Requires >1 infusion for complete resolution; or

    None: No improvement or condition worsens.


  • Annualized Rate of Bleeding Episodes [ Time Frame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: No ]
    Number of bleeding episodes per subject annualized over 1 year for all etiologies

  • Weekly rAHF-PFM Utilization [ Time Frame: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: No ]

    Weight-Adjusted Weekly Dose for Prophylaxis, On-Demand Treatment, and Perioperative Management.

    rAHF-PFM dose determined by the investigator (ie: standard regimen [25-50 IU/kg body weight, 3-4 times per week]; modified prophylactic regimen [dose and frequency selected by investigator] or on-demand treatment [dose selected by investigator]). Dosing to treat BEs was at investigator's discretion and in accordance with institution's standard of care.

    rAHF-PFM was administered I.V. via bolus infusion, except for perioperative management when it was given either by continuous or bolus infusion.


  • In Vivo Incremental Recovery [ Time Frame: 30 minutes pre-infusion to 30 minutes post-infusion ] [ Designated as safety issue: No ]
    Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits.

  • Assessment of Intra-operative Hemostasis [ Time Frame: Assessed at the time of discharge from recovery room ] [ Designated as safety issue: No ]

    Number of surgical procedures managed with rAHF-PFM and with surgeon's assessment of hemostasis based on a 4-point ordinal scale:

    Excellent: ≤ average predicted blood loss for matched procedures in healthy individuals

    Good: > average predicted blood loss, but ≤ maximal predicted blood loss for matched procedures in healthy individuals

    Fair: > maximal predicted blood loss for matched procedures in healthy individuals, and hemostasis was achieved

    None: uncontrolled hemostasis with proper dosing, necessitating a change in treatment regimen


  • Assessment of Postoperative Hemostasis [ Time Frame: Assessed at the time of discharge from hospital or clinic ] [ Designated as safety issue: No ]

    Number of surgical procedures managed with rAHF-PFM and with investigator's assessment of hemostasis based on a 4-point ordinal scale:

    Excellent: hemostasis was as good as or better than other licensed factor VIII products for matched procedure

    Good: hemostasis was probably as good as other licensed factor VIII products for matched procedure

    Fair: hemostasis was clearly < optimal for matched procedure, without need to change regimen

    None: bleeding from inadequate response with proper dosing, necessitating a change in regimen


  • Assessment of Blood Loss During Surgical Procedures [ Time Frame: Predicted volumes preoperatively estimated and actual volumes intraoperatively recorded ] [ Designated as safety issue: No ]
    Percentage of actual intraoperative blood loss compared to preoperatively predicted average and maximal blood loss in hemostatically normal matched individuals (from institutional blood bank records)

  • Adverse Events Deemed Related to Treatment [ Time Frame: Reported during the study period which was to be at least 75 exposure days or 3 years (whichever came first) ] [ Designated as safety issue: Yes ]
    Percentage of participants who reported AEs deemed related to treatment with rAHF-PFM

  • Development of Antibodies to Heterologous Proteins [ Time Frame: Assessed at baseline, throughout the duration of the study, which was to be at least 75 exposure days or 3 years (whichever came first), and at the termination visit. ] [ Designated as safety issue: Yes ]
    Percentage of treated participants who developed antibodies to heterologous proteins (ie, Chinese Hamster Ovary Cell Protein, Murine IgG, or Recombinant Human VWF)


Enrollment: 66
Study Start Date: April 2004
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm - All Participants Biological: Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)

Treatment regimens were determined by the investigator, and may have been any combination of standard prophylaxis (25 to 50 IU/kg body weight, 3 to 4 times per week), investigator-determined prophylaxis, and/or on-demand treatment (dose selected by investigator).

The treatment of bleeding episodes and perioperative management was at the discretion of the investigator and consistent with the institution's standard of care.

For incremental recovery assessments, a single infusion at 50 +/- 5 IU/kg was to be given.

Immune tolerance induction (ITI) therapy for subjects who developed factor VIII inhibitors was at the discretion of the investigator, based on the institution's guidelines or described in peer-reviewed literature, and was to be approved by the sponsor's medical director.

rAHF-PFM was to be administered intravenously via bolus infusion, except for perioperative management when it may have been given either by continuous or bolus infusion.

  Eligibility

Ages Eligible for Study:   up to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as documented at screening
  • The subject is < 6 years of age
  • The subject's legally authorized representative has provided written informed consent

Exclusion Criteria:

  • The subject has a history of exposure to factor VIII other than rAHF PFM or more than 3 infusions of commercially available rAHF PFM (i.e., ADVATE) within 28 days prior to screening, as determined by the subject's medical history. Any infusion of factor VIII replacement products prior to the 28-day period excludes the subject from participation
  • The subject has received more than 3 infusions of rAHF PFM (commercially available and/or study product) between screening and prior to the initial recovery infusion
  • The subject has a detectable inhibitor to factor VIII, as measured in the screening sample by the Nijmegen assay in the central laboratory
  • The subject has a history of inhibitor to factor VIII at any time prior to screening
  • The subject has a known hypersensitivity to rAHF PFM

  • The subject has any 1 of the following laboratory abnormalities at the time of screening:

    1. Platelet count < 100,000/mm^3
    2. Hemoglobin concentration < 10 g/dL (100 g/L)
    3. Serum creatinine > 1.5 times the upper limit of normal (ULN) for age
    4. Total bilirubin > 2 times the ULN for age
  • The subject has an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's disease)
  • The subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), as determined by the subject's medical history
  • At the time of enrollment, the subject has a clinically significant chronic disease other than hemophilia A
  • The subject is currently participating in another investigational drug study, or has participated in any clinical study involving an investigational drug within 120 days of the screening visit
  • The subject (or the subject's legally authorized representative) is identified by the investigator as being unable or unwilling to cooperate with study procedures
  • The subject has received any blood product, including packed red blood cells (RBC), platelets, plasma, or cryoprecipitate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00157157

  Show 35 Study Locations
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Principal Investigator: Baxter BioScience Investigator Baxter BioScience
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00157157     History of Changes
Other Study ID Numbers: 060103
Study First Received: September 9, 2005
Results First Received: February 15, 2011
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Austria: Federal Ministry for Health and Women
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ministry of Health
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Baxter Healthcare Corporation:
Factor VIII Deficiency

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
 Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013