Efficacy and Safety Study of Prophylactic Versus On-Demand Treatment With Feiba NF in Subjects With Hemophilia A or B and a High Titer Inhibitor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00851721
First received: February 25, 2009
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

The purpose of the study was to determine the efficacy, safety, and health-related quality of life benefits with FEIBA NF prophylactic treatment as compared with on-demand treatment.


Condition Intervention Phase
Hemophilia A
Hemophilia B
(High-titer) Factor VIII Inhibitor
(High-titer) Factor IX Inhibitor
Biological: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: FEIBA NF: A Prospective, Open-label, Randomized, Parallel Study to Evaluate the Efficacy and Safety of Prophylactic Versus On-Demand Treatment in Subjects With Hemophilia A or B and a High Titer Inhibitor

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    Participants were Randomized to Receive 1 of the 2 Following Treatment Regimens:

    1. On-Demand: FEIBA NF dose & dosing interval as prescribed by treating physician
    2. Prophylaxis: 85 ± 15 U/kg of FEIBA NF every other day during 12-month prophylactic period

    Annualized rate of bleeding episodes was calculated as:

    (Number of bleeding episodes/observed treatment period in days) * 365.25



Secondary Outcome Measures:
  • Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
    Spontaneous includes unknown/undermined etiology

  • Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    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.

    The difference in mean transformed ABRs was used to perform statistical tests and generate p-values at a significance level of 5%

    Participants were Randomized to Receive 1 of the 2 Following Treatment Regimens:

    1. On-Demand: FEIBA NF dose & dosing interval as prescribed by treating physician
    2. Prophylaxis: 85 ± 15 U/kg of FEIBA NF every other day during 12-month prophylactic period

  • Annualized Bleeding Rate for New Target Joints [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
    Target joints are ≥4 bleeds/6 months in any one of the following joints: ankles, knees, elbows, and hips; a target joint bleeding episode refers to an individual anatomical location.

  • Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    Annualized bleed rates (ABRs) 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 a two-sample, two-sided t-test.

    The difference in mean transformed ABRs was used to perform statistical tests and generate p-values at a significance level of 5%


  • Number of New Target Joints [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
    Target Joints are defined as ≥4 bleeds/6 months in any one of the following joints: ankles, knees, elbows and hips

  • Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 Years Old) [ Time Frame: Throughout the study period, 12 months ± 14 days ] [ Designated as safety issue: No ]

    Pain caused by a bleeding episode in adolescents and adults (≥12 years old) was measured at pre-infusion (pre-inf) and at 6 ± 0.5 hours (h) and 24 ± 1 h post-infusion (post-inf) (after the last infusion given to treat a bleeding episode) on the VAS pain scale in millimeters from 0 (no pain) to 100 (worst possible pain). For analysis purposes, if short acting analgesics (duration of activity approximately 6 ± 0.5 h) were used, pain was assigned the highest possible score (100). Pain assessment occurred after each infusion related to single bleeding episodes. In case participants required an additional infusion within 24h, pain was assessed 6 ± 0.5 h and 24 ±1 h following the subsequent infusion.

    Change in VAS scores at 6 ± 0.5 h and 24 ±1 h post-infusion were also compared relative to pre-infusion VAS scores (ie, (pre-infusion VAS score) - (post-infusion VAS score)).


  • Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 Years Old) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    Pain caused by a bleeding episode (BE) in pediatric participants (<12 years old) was measured at pre-infusion (pre-inf) and at 6 ± 0.5 h and 24 ± 1 h post-infusion (post-inf) (after the last infusion given to treat a bleeding episode) using the children's VAS pain scale (a facial expression scale with one end marked as no pain and the opposite end marked as the worst possible pain). For analysis purposes, if short acting analgesics (duration of activity approximately 6 ± 0.5 h) were used, pain was assigned the highest possible score (worst possible pain).

    Scores on the children's VAS scale are presented as:

    • No Pain
    • Mild Pain
    • Moderate pain
    • Severe pain
    • Very severe pain

  • Assessment of Clinical Symptoms - Range of Motion (ROM) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
    ROM was measured using a goniometer for 3 key joints (ie, ankles, knees, and elbows) at screening, month 6, and termination (end of study visit)

  • Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 Hours [ Time Frame: 6 h ± 30 min post-infusion ] [ Designated as safety issue: No ]

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

    Excellent: Full pain relief & bleeding cessation within ~6 hours of 1 infusion. Additional infusions may have been given to maintain hemostasis;

    Good: Definite pain relief and/or improvement in bleeding within ~6 hours after infusion. Possibly requires >1 infusion for complete resolution;

    Fair: Probable or slight relief of pain & slight improvement in bleeding within

    ~6 hours after infusion. Requires >1 infusion for complete resolution;

    None: No improvement or condition worsens


  • Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 Hours [ Time Frame: 24 ± 1 h post-infusion ] [ Designated as safety issue: No ]

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

    Excellent: Full pain relief & bleeding cessation within ~24 hours of 1 infusion. Additional infusions may have been given to maintain hemostasis;

    Good: Definite pain relief and/or improvement in bleeding within ~24 hours after infusion. Possibly requires >1 infusion for complete resolution;

    Fair: Probable or slight relief of pain & slight improvement in bleeding within

    ~24 hours after infusion. Requires >1 infusion for complete resolution;

    None: No improvement or condition worsens


  • Total Weight Adjusted Dose to Control a Bleeding Episode [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for aPTT is 22.8 - 31 seconds.

  • Abnormal D-Dimer Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for D-dimers is <500 ng/mL.

  • Abnormal Fibrinogen Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for fibrinogen is 200-400 mg/dL.

  • Abnormal Fibrin Degradation Products (FDP) Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for FDP is 0-5 ug/mL.

  • Abnormal Prothrombin Fragment F 1.2 Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for prothrombin fragment F 1.2 is 69-229 pmol/L.

  • Abnormal Prothrombin Time Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for PT is 9.7-12.3 sec.

  • Abnormal Thrombin-Antithrombin III (TAT) Assay Results [ Time Frame: Screening visit, Month 3, Month 6, Month 9, and Termination visit ] [ Designated as safety issue: Yes ]
    The normal reference range of values for TAT is 1-4.1 ug/L.

  • Viral Serology From Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]
    • Hepatitis A Virus Antibody (HAV Ab)
    • Hepatitis B Virus Core Antibody (HBcAb)
    • Hepatitis B Virus Surface Antibody (HBsAb)
    • Hepatitis B Virus Surface Antigen (HBsAg)
    • Hepatitis C Virus (HCV)

  • Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]
  • Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV] [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]

    Normal range (0 - 0.89 IV); High (> 0.89 IV)

    - Parvovirus B19 IgG Antibody [IV] (Parvo IgG Ab)


  • Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV] [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]

    Normal range (0 - 0.89 IV); High (> 0.89 IV)

    - Parvovirus B19 IgM Antibody [IV] (Parvo IgM Ab)


  • Rate of Related Adverse Events (AEs) Per Year [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]
  • Rate of Related Adverse Events (AEs) During or Within 1 Hour of Infusion Per Year [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]
  • Number of Related Thromboembolic Adverse Events (AEs) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]
  • Absolute Changes in Inhibitor Titer of Hemophilia A Participants With Shifts in Factor VIII (FVIII) Inhibitor Titer Levels [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]

    Absolute Changes in Inhibitor Titer (or no change in low or high titer status):

    • Inhibitor Titer went from Low (≤5 BU) to Low (≤5 BU)
    • Inhibitor Titer went from Low (≤5 BU) to High (>5 BU)
    • Inhibitor Titer went from High (>5 BU) to Low (≤5 BU)
    • Inhibitor Titer went from High (>5 BU) to High (>5 BU)

  • Absolute Changes in Inhibitor Titer of Hemophilia B Participants With Shifts in Factor IX (FIX) Inhibitor Titer Levels [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: Yes ]

    Absolute Changes in Inhibitor Titer (or no change in low or high titer status):

    • Inhibitor Titer went from Low (≤5 BU) to Low (≤5 BU)
    • Inhibitor Titer went from Low (≤5 BU) to High (>5 BU)
    • Inhibitor Titer went from High (>5 BU) to Low (≤5 BU)
    • Inhibitor Titer went from High (>5 BU) to High (>5 BU)

  • Pharmacoeconomics: Annual Days Lost Due to Bleeding (Work or School) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Number of Hospitalizations for Bleeding [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Number of Hospitalizations for Indwelling Line [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Number of Emergency Room Visits [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Number of Physician's Office Visits [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Total Length of Hospitalization for Bleeding [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Total Length of Hospitalization for Indwelling Line [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Pharmacoeconomics: Annual Total Number of Days Lost (Work or School) [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]
  • Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

    EQ-5D Index scores based on EQ-5D questionnaire were calculated for participants ≥14 years of age, at screening, 6 months, and at termination visit. Changes in scores at 6 months and termination were also calculated.

    A relatively higher score represents better quality of life.


  • Hemophilia-specific Quality of Life Questionnaire for Adults (Haem-A-QoL) ≥ 16 Years Old [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    The Haem-A-QoL instrument has been developed and used in Hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: Physical Health (PH), Sports & Leisure (S&L), School & Work (W&S), Dealing with Hemophilia (Dealing), Family Planning (FP), Feeling, Relationships (R'ships), Treatment, View, and Outlook for the Future (Future). A Haem-A-QoL Total Score (Total) was also calculated. For the Haem-A-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

    Haem-A-QoL scores at screening, 6 months, and at termination visit were collected. Changes in scores at 6 months and termination were also calculated.


  • Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: Physical Health (PH), Sports & School (S&S), Dealing with Hemophilia (Dealing), Family, Feeling, Relationships (R'ships), Treatment, View, Outlook for the Future (Future), Friends, Others, and Support. A Haemo-QoL Total Score (Total) was also calculated. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

    Haemo-QoL scores at screening, 6 months, and at termination visit were collected. Changes in scores at 6 months and termination were also calculated.


  • Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation [ Time Frame: 12 months ± 14 days ] [ Designated as safety issue: No ]

    The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: Physical Health (PH), Sports & School (S&S), Dealing with Hemophilia (Dealing), Family, Feeling, Relationships (R'ships), Treatment, View, Outlook for the Future (Future), Friends, Others, and Support. A Haemo-QoL Total Score (Total) was also calculated. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

    Haemo-QoL scores at screening, 6 months, and at termination visit were collected. Changes in scores at 6 months and termination were also calculated.


  • Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents ≥12 Years Old [ Time Frame: Baseline, 6 months and 12 months ± 14 days ] [ Designated as safety issue: No ]

    General pain was assessed using a VAS pain scale at screening, 6 months, and at termination. Unlike the VAS pain assessment for pain of bleeding episodes (Outcome above), this general pain assessment did not take use of analgesics into account. For the pain scale, a higher number indicates worse pain.

    The visual analog scale ranges from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (=0) and 'Best imaginable health state' (=100). A positive change from baseline indicates improvement.

    Change in VAS scores at 6 months and study termination were also compared relative to Baseline/Screening scores (ie, (Baseline/Screening VAS score) - (VAS score at 6 months and study termination).


  • Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old [ Time Frame: Baseline, 6 months and 12 months ± 14 days ] [ Designated as safety issue: No ]

    General pain was assessed using the children's VAS pain scale (a facial expression scale with one end marked as no pain and the opposite end marked as the worst possible pain). Assessments were done at the screening, 6 months, and termination visits.

    Scores on the children's VAS scale are presented as:

    • No Pain
    • Mild Pain
    • Moderate pain
    • Severe pain
    • Very severe pain

    Unlike the VAS pain assessment for pain of bleeding episodes (Outcome above), this general pain assessment did not take use of analgesics into account.

    Change in VAS scores at 6 months and study termination were also compared relative to Baseline/Screening scores (ie, (Baseline/Screening VAS score) - (VAS score at 6 months and study termination).



Enrollment: 52
Study Start Date: March 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prophylaxis arm Biological: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
85 ± 15 U/kg of FEIBA NF every other day during the 12-month prophylactic period
Other Name: FEIBA NF
Active Comparator: On-demand arm Biological: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
FEIBA NF dose and dosing interval as prescribed by the treating physician
Other Name: FEIBA NF

  Eligibility

Ages Eligible for Study:   4 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent form by the participant or the participant's legally authorized representative
  • The participant is ≥ 4 to ≤ 65 years of age
  • The participant has a Karnofsky performance score of ≥ 60
  • Hemophilia A and B of any severity, with documented history of high-titer inhibitor (> 5 Bethesda unit (BU)) for at least 12 months; or, if inhibitor titer is ≤ 5 BU, and the participant is refractory with increased dosing of either factor VIII (FVIII) or factor IX (FIX), as demonstrated from the participant's medical history
  • Currently being treated on an on-demand basis for treatment of bleeding episodes
  • Adequate venous access, with or without central venous device
  • ≥ 12 bleeding episodes requiring treatment with by-passing agents in the past 12 months, based on medical history
  • Competent in-home treatment and infusion therapy
  • Currently using bypassing agents (activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFVIIa)) for treatment of bleeding episodes
  • HCV-, either by antibody testing or polymerase chain reaction (PCR); or HCV+ with stable hepatic disease
  • HIV-, or HIV+ with stable disease and CD4 count > 200 cells/mm3 at screening
  • Female participant of childbearing potential, presents with a negative serum pregnancy test, and agrees to employ adequate birth control measures for the duration of the study

Exclusion Criteria:

  • Currently receiving immune tolerance induction (ITI)
  • Currently on regular prophylactic therapy to prevent bleeding episodes
  • Clinically symptomatic liver disease (e.g. diagnosis of cirrhosis [confirmed by liver biopsy], portal vein hypertension, ascites, prothrombin time (PT) 5 seconds above upper limit of normal)
  • Platelet count < 100,000/ml
  • Planned elective surgery during participation in this study
  • Participant is currently participating in another clinical study and has received an investigational product or device within 30 days prior to study entry
  • Planned use of pegylated or non-pegylated alpha-interferon with or without ribavirin for HCV infected participants or planned use of a protease inhibitor for HIV infected participants. Participants currently taking any of these medications for a 30-day course are eligible.
  • Clinically significant increase in D-dimer levels from historical baseline and/or associated with chronic liver disease or clinically evident thromboembolic event
  • Known hypersensitivity to anti-inhibitor coagulant complexes (AICCs)
  • Currently treated with a systemic immunomodulating drug
  • Prior history of thromboembolic event: acute myocardial infarction, deep vein thrombosis, or pulmonary embolism
  • Diagnosis of advanced atherosclerosis, malignancy and/or other diseases that may increase the participant's risk of thromboembolic complications
  • Clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851721

Locations
United States, Illinois
Chicago, Illinois, United States
United States, Ohio
Cleveland, Ohio, United States
Brazil
Rio de Janeiro, RJ, Brazil
Sao Paulo, SP, Brazil
Bulgaria
Sofia, Bulgaria
Croatia
Zagreb, Croatia
Japan
Kanagawa, Japan
Nara, Japan
New Zealand
Wellington, New Zealand
Poland
Krakow, Poland
Warsaw, Poland
Romania
Bucharest, Romania
Timisoara, Romania
Russian Federation
Ekaterinburg, Russian Federation
Kirov, Russian Federation
Moscow, Russian Federation
Ukraine
Lviv, Ukraine
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Wing-Yen Wong, MD Baxter Healthcare Corporation
  More Information

Publications:
Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00851721     History of Changes
Other Study ID Numbers: 090701
Study First Received: February 25, 2009
Results First Received: January 30, 2014
Last Updated: January 30, 2014
Health Authority: Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Croatia: Agency for Medicinal Product and Medical Devices
Japan: Pharmaceuticals and Medical Devices Agency
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: FSI Scientific Center of Expertise of Medical Application
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by Baxter Healthcare Corporation:
Hemophilia A
Hemophilia B
Factor VIII Inhibitor
Factor IX Inhibitor

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

ClinicalTrials.gov processed this record on October 19, 2014