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BAX 326 Pediatric Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxalta US Inc.
ClinicalTrials.gov Identifier:
NCT01488994
First received: December 6, 2011
Last updated: July 21, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to assess BAX 326 pharmacokinetic parameters, to evaluate its hemostatic efficacy, safety, immunogenicity, and changes in health-related quality of life in pediatric patients.

Condition Intervention Phase
Hemophilia B
Biological: BAX326
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BAX 326 (Recombinant Factor IX): A Phase 2/3 Prospective, Uncontrolled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity in Previously Treated Pediatric Patients With Severe (FIX Level < 1%) or Moderately Severe (FIX Level 1-2%) Hemophilia B

Resource links provided by NLM:


Further study details as provided by Baxalta US Inc.:

Primary Outcome Measures:
  • Adverse Events (AEs) Possibly or Probably Related to BAX326 [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion Per Dose (AUC 0-72h/Dose) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Mean Residence Time (MRT) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. ] [ Designated as safety issue: No ]
    Computed as total area under the first moment curve (total AUMC) divided by the total area under the concentration versus time curve (total AUC)

  • Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. ] [ Designated as safety issue: No ]
    Computed as the dose divided by total Area under the curve (AUC)

  • Pharmacokinetics (PK): Incremental Recovery (IR) [ Time Frame: Within 30 mins pre-infusion and 30 mins post-infusion ] [ Designated as safety issue: No ]
    The rise in FIX activity in IU/dL per unit dose administered in IU/kg. Calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose

  • Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. ] [ Designated as safety issue: No ]
    Calculated as log_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model

  • Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) [ Time Frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. ] [ Designated as safety issue: No ]
    Computed as Clearance (CL) * Mean residence time (MRT)

  • Pharmacokinetics (PK): Incremental Recovery (IR) Over Time [ Time Frame: Within 30 mins pre-infusion and 30 mins post-infusion at baseline, Week 5, Week 13 and Week 26. ] [ Designated as safety issue: No ]

    IR calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose. IR is determined at baseline (PK analysis), Week 5, Week 13 and Week 26 timepoints.

    Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants > 6 years of age; pediatric participants 6 to <12 years of age; pharmacokinetic Full Analysis Set (PKFAS).


  • Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
  • Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]

    Rating Scale for Treatment of bleeding episodes (4-point ordinal scale):

    • Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring.
    • Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution.
    • Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution.
    • None: No improvement or condition worsens.

  • Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR) [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]

    The annualized bleeding rate (ABR) during prophylaxis was calculated only for participants who had adequate treatment time for bleeding rate assessment (i.e., more than 3 months of prophylaxis treatment). The observation period for prophylaxis was to be the time between the first and the last prophylactic infusions. The treatment period for surgery was to be excluded from the bleed rate calculation.

    ABR calculated as (Number of bleeding episodes/observed treatment period in days) * 365.25.


  • Consumption of BAX326: Number of Infusions Per Month [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
  • Consumption of BAX326: Number of Infusions Per Year [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
  • Consumption of BAX326: Weight-adjusted Consumption Per Month [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
  • Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized) [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
  • Consumption of BAX326: Weight-adjusted Consumption Per Event [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: No ]
    Event includes prophylactic infusions of study product and infusions of study product for treatment of bleeding episodes (BEs).

  • Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]
  • Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]

    If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay.

    AB=antibodies in category for outcome measure data.


  • Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]
  • Safety: Number of Participants With Thrombotic Events [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]
  • Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]

    Categories consist of Clinically Significant (CS) changes in haemaotology parameters, clinical chemistry parameters and vital signs.

    Abbreviations in categories; Clin=clinical; params=parameters


  • Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) [ Time Frame: Throughout study period (approximately 17 months) ] [ Designated as safety issue: Yes ]
    If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay.

  • Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

    For this study, the PedsQL™ questionnaires for participants 2 to 7 years of age (parent-proxy versions for age groups 2-4 years and 5-7 years) and PedsQL™ Child version for participants 8 to 12 years of age were used.

    The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. A 5-point score is used for each domain: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0 so that higher scores indicate better quality of life (QoL). The total score is the mean (average) of all scores from the 4 domains.

    The change from baseline in total score is reported- a positive score indicates a better QoL compared to baseline and a negative score indicates a poorer QoL compared to baseline.


  • Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score [ Time Frame: Baseline and 6 months ] [ 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. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

  • Health Resource Use: Number of Hospitalizations [ Time Frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 ] [ Designated as safety issue: No ]
    The number of hospitalizations per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.

  • Health Resource Use: Length of Hospitalization [ Time Frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 ] [ Designated as safety issue: No ]
    The length of hospitalization per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.

  • Health Resource Use: Unscheduled Doctor's Office Visits [ Time Frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 ] [ Designated as safety issue: No ]
    The number of unscheduled doctor's Office visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.

  • Health Resource Use: Emergency Room Visits [ Time Frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 ] [ Designated as safety issue: No ]
    The number of Emergency Room visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.

  • Health Resource Use: Days Lost From School [ Time Frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 ] [ Designated as safety issue: No ]
    The number of days lost from school per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.


Enrollment: 23
Study Start Date: December 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAX326 < 6 years of age Biological: BAX326
All participants underwent a pharmacokinetic evaluation with BAX326 (recombinant Factor IX) followed by twice weekly prophylactic treatment for 6 months or for at least 50 exposure days, whichever occurred last.
Other Names:
  • BAX 326
  • RIXUBIS
Experimental: BAX326 6 to <12 years of age Biological: BAX326
All participants underwent a pharmacokinetic evaluation with BAX326 (recombinant Factor IX) followed by twice weekly prophylactic treatment for 6 months or for at least 50 exposure days, whichever occurred last.
Other Names:
  • BAX 326
  • RIXUBIS

Detailed Description:
The secondary outcome measure: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours (h) Post-infusion analysis was not done due to the different time-points for the last PK blood sample, AUC0-72 h was redundant and only total AUC was included in the PK analysis.
  Eligibility

Ages Eligible for Study:   up to 12 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Participant and/or legal representative has/have voluntarily provided signed informed consent
  • Participant has severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B
  • Participant is < 12 years old at the time of screening
  • Participant has no evidence of a history of FIX inhibitors (based on the participant's medical records)
  • Participant is immunocompetent as evidenced by a CD4 count ≥ 200 cells/mm^3

Main Exclusion Criteria:

  • Participant has a detectable FIX inhibitor at screening, with a titer ≥ 0.6 Bethesda Unit (BU)
  • Participant has a history of allergic reaction, e.g. anaphylaxis, following exposure to FIX concentrate(s)
  • Participant has evidence of an ongoing or recent thrombotic disease
  • Participant has an inherited or acquired hemostatic defect other than hemophilia B
  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: NCT01488994

Locations
India
LNJP Maulana Azad Medical College & Associated Hospitals
New Delhi, India, 110002
Poland
University Pediatric Hospital
Cracow, Poland, 30-663
Stanislaw Popowski Provincial Specialist Pediatric Hospital
Olsztyn, Poland, 10-561
Professor Tadeusz Sokolowski Independent Public Teaching Hospital of the Pomeranian Medical University in Szczecin
Szczecin, Poland, 71-252
Romania
S.C. Sanador SRL
Bucharest, Romania, 11156
Louis Turcanu Emergency Children's Hospital
Timisoara, Romania, 300011
Russian Federation
Regional Clinical Hospital
Ekaterinburg, Russian Federation, 620149
Pediatric Regional Clinical Hospital, Hematology Department
Krasnodar, Russian Federation, 350007
Republican Center for Hemophilia Treatment
St. Petersburg, Russian Federation, 195213
Ukraine
State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine"
Lviv, Ukraine, 79044
United Kingdom
Manchester Children´s Hospital
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Baxalta US Inc.
Investigators
Study Director: Baxalta Study Director Baxalta US Inc.
  More Information

Responsible Party: Baxalta US Inc.
ClinicalTrials.gov Identifier: NCT01488994     History of Changes
Other Study ID Numbers: 251101  2011-002437-19 
Study First Received: December 6, 2011
Results First Received: March 24, 2016
Last Updated: July 21, 2016
Health Authority: United States: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
Russia: FSI Scientific Center of Expertise of Medical Application
Romania: National Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India

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

ClinicalTrials.gov processed this record on September 26, 2016