BAX 326 Pediatric Study

This study has been completed.
Sponsor:
Collaborator:
Baxter Innovations GmbH
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01488994
First received: December 6, 2011
Last updated: May 29, 2014
Last verified: May 2014
  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: Recombinant Factor IX
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 <= 2%) Hemophilia B

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Adverse events possibly or probably related to BAX 326 [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve from 0 to 72 hours post-infusion [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ Designated as safety issue: No ]
  • Total Area under the plasma concentration versus time curve per dose (Total AUC/dose) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ Designated as safety issue: No ]
  • Mean residence time (MRT) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ 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)

  • Factor IX (FIX) Clearance(CL) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ Designated as safety issue: No ]
    Computed as the dose divided by total AUC

  • Incremental recovery (IR) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ Designated as safety issue: No ]
    Change in factor VIII concentration from pre-infusion post-infusion

  • Elimination phase half-life (T 1/2) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ 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

  • Volume of distribution at steady state (Vss) [ Time Frame: 7 post-infusion time points over a period up to 72 hours ] [ Designated as safety issue: No ]
    Computed as Clearance (CL) * Mean residence time (MRT)

  • Incremental recovery (IR) over time [ Time Frame: Week 5, Week 13, Week 26 and study completion/termination visit (for participants receiving BAX326 beyond Week 26) ] [ Designated as safety issue: No ]
  • Hemostatic efficacy of the acute management of bleeding episodes [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Efficacy assessments: Determination of factor IX level and pharmacokinetic parameters at certain time points, including incremental recovery; rating scale for treatment of bleeding episodes (excellent / good / fair / none)

  • Treatment of bleeding episodes: number of infusions per bleeding episode [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]
  • Treatment of bleeding episodes (BEs): overall hemostatic efficacy rating at resolution of bleed [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]

    Rating Scale for Treatment of BEs (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.

  • Prophylaxis: Annualized bleeding rate [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]
  • Consumption of BAX326: number of infusions [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]
  • Consumption of BAX326: weight-adjusted consumption [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]
  • Consumption of BAX326: weight-adjusted consumption per event [ Time Frame: 26 (+/- 1) weeks ] [ Designated as safety issue: No ]
  • Development of inhibitory antibodies to FIX [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Development of total binding antibodies to FIX [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Occurrence of severe allergic reactions, e.g. anaphylaxis [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Occurrence of thrombotic events [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Clinically significant changes in routine laboratory parameters (hematology and clinical chemistry), and vital signs [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Development of antibodies to Chinese hamster ovary (CHO) proteins and recombinant furin (rFurin) [ Time Frame: 7 months (per subject) ] [ Designated as safety issue: Yes ]
  • Health-related Quality of Life Outcome Measure: Generic: PedsQL™ (Parent-proxy versions: age group 2-4 years and age group 5-7 years) [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
  • Health-related Quality of Life Outcome Measure: Hospitalizations [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Age group <6 years of age

  • Health-related Quality of Life Outcome Measure: Length of Hospitalizations [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Age group <6 years of age

  • Health-related Quality of Life Outcome Measure: Emergency Room Visits [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Age group <6 years of age

  • Health-related Quality of Life Outcome Measure: Unscheduled Office Visits [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Age group <6 years of age

  • Health-related Quality of Life Outcome Measure: Days Lost from School [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    Age group <6 years of age

  • Health-related Quality of Life Outcome Measure: Disease-specific: Haemo-QoL, short version: age group 8 to 11 years of age [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
  • Health-related Quality of Life Outcome Measure: Generic- PedsQL™ Child version: age group 8 to 11 years of age [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
  • Health-related Quality of Life Outcome Measure: Hospitalizations [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    6 - <12 years

  • Health-related Quality of Life Outcome Measure: Length of Hospitalizations [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    6 - <12 years

  • Health-related Quality of Life Outcome Measure: Emergency Room Visits [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    6 - <12 years

  • Health-related Quality of Life Outcome Measure: Unscheduled Office Visits [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    6 - <12 years

  • Health-related Quality of Life Outcome Measure: Days Lost from School [ Time Frame: 26 (+/-1) weeks ] [ Designated as safety issue: No ]
    6 - <12 years


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 Biological: Recombinant Factor IX
Participants underwent a pharmacokinetic evaluation with recombinant Factor IX prior to starting a twice weekly prophylactic treatment.
Other Names:
  • RIXUBIS
  • BAX 326

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
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
Baxter Healthcare Corporation
Baxter Innovations GmbH
Investigators
Study Director: Srilatha Tangada, PhD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01488994     History of Changes
Other Study ID Numbers: 251101, 2011-002437-19
Study First Received: December 6, 2011
Last Updated: May 29, 2014
Health Authority: India: Drugs Controller General of India
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 Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hemophilia B
Hemophilia A
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 July 22, 2014