BAX 326 Surgery Study in Hemophilia B Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxalta US Inc.
ClinicalTrials.gov Identifier:
NCT01507896
First received: January 9, 2012
Last updated: July 26, 2016
Last verified: July 2016

January 9, 2012
July 26, 2016
December 2011
May 2014   (final data collection date for primary outcome measure)
  • Intraoperative Hemostatic Efficacy [ Time Frame: On day of surgery ] [ Designated as safety issue: No ]

    Assessment by the operating surgeon on a 4 point ordinal scale (according to the definitions provided below):

    • Excellent: Intraoperative blood loss was less than or equal to that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% )
    • Good: Intraoperative blood loss was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101 - 150%)
    • Fair: Intraoperative blood loss was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%)
    • None: Uncontrolled hemorrhage that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate
  • Actual Intraoperative Blood Loss [ Time Frame: On day of surgery ] [ Designated as safety issue: No ]
    Actual intraoperative blood loss was determined by the drainage volume, if a drain was placed, and the estimated blood loss into swabs and towels during the procedure.
  • Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon [ Time Frame: On day of surgery ] [ Designated as safety issue: No ]
    Predicted average/maximum blood loss minus actual blood loss.
  • Postoperative Hemostatic Efficacy at Drain Removal [ Time Frame: At drain removal (from 1-3 days postoperatively) ] [ Designated as safety issue: No ]

    The postoperative hemostatic efficacy was to be assessed by the operating surgeon according to the following criteria (4-point ordinal scale):

    • Excellent: Volume in drain was less than or equal than that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% )
    • Good: Volume in drain was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101% - 150%)
    • Fair: Volume in drain was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%)
    • None: Uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate
  • Postoperative Hemostatic Efficacy at Postoperative Day 3 [ Time Frame: At postoperative day 3 (approximately 72 hours postoperatively) ] [ Designated as safety issue: No ]

    Assessment by the operating surgeon on a 4 point ordinal scale:

    • Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant
    • Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant
    • Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate
    • None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate
  • Postoperative Hemostatic Efficacy on Day of Discharge [ Time Frame: At discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) ] [ Designated as safety issue: No ]

    Assessment by the operating surgeon on a 4 point ordinal scale:

    • Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant
    • Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant
    • Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate
    • None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate
  • Actual Postoperative Blood Loss [ Time Frame: At drain removal (from 1-3 days postoperatively) ] [ Designated as safety issue: No ]
    Postoperative blood loss was based on the drainage fluid and was only assessed for participants who had a drain placed during surgery.
  • Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon [ Time Frame: At postoperative day 3 (approximately 72 hours postoperatively) ] [ Designated as safety issue: No ]
    Predicted average/maximum blood loss minus actual blood loss for participants who had a drain placed during surgery.
  • Daily Weight-Adjusted Dose of BAX326 Per Participant [ Time Frame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) ] [ Designated as safety issue: No ]

    Daily weight-adjusted doses of BAX326 per participant were recorded from the day of surgery until postoperative Days 11+.

    Each category in outcome measure includes number of all, major and minor surgeries, respectively, if different from the totals.

  • Total Weight-Adjusted Dose of BAX326 Per Participant [ Time Frame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) ] [ Designated as safety issue: No ]
    Assessed for the intra- and postoperative periods.
  • Number of Units of Blood Product Transfused [ Time Frame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) ] [ Designated as safety issue: No ]
    Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.
  • Volume of Blood Product Transfused [ Time Frame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) ] [ Designated as safety issue: No ]
    Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.
  • Safety: Number of Participants who Developed Inhibitory Antibodies to Factor IX (FIX) [ Time Frame: Throughout the study period (approximately 2 years 5 months) ] [ Designated as safety issue: Yes ]
  • Safety: Number of Participants who Developed Total Binding Antibodies to Factor IX (FIX) [ Time Frame: Throughout the study period (approximately 2 years 5 months) ] [ Designated as safety issue: Yes ]
    If there was more than 2-dilution increase as compared to pre-study level at screening.
  • Safety: Number of Adverse events Related to BAX326 [ Time Frame: Throughout the study period (approximately 2 years 5 months) ] [ Designated as safety issue: Yes ]
  • Safety: Number of Participants Who Have the Occurence of a Thrombotic Event [ Time Frame: Throughout the study period (approximately 2 years 5 months) ] [ Designated as safety issue: Yes ]
  • Presurgical Pharmacokinetics (PK): Area under the plasma concentration versus time curve (AUC) from 0 to 72 hours post-infusion per dose [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    AUC0-72h (area under the plasma concentration/time curve from time 0 to 72 hours) was computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R2.
  • Presurgical Pharmacokinetics (PK): Total Area under the plasma concentration versus time curve per dose (Total AUC/dose) [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    Total AUC/Dose is also AUC0-inf (area under the plasma concentration/time curve from time 0 to infinity) and was defined as AUC0-t + Ct / λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration and λz is the terminal rate constant.
  • Presurgical Pharmacokinetics (PK): Mean residence time (MRT) [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    The MRT is the average time that the study product stays in the body (or plasma) and is calculated as: AUMC 0-inf / AUC 0-inf, where AUMC 0-inf was determined in a similar manner as AUC 0-inf.
  • Presurgical Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    CL is the volume of plasma which is completely cleared of study product per unit time and is calculated as the dose divided by the total area under the curve from 0 to infinity (AUC0-inf).
  • Presurgical Pharmacokinetics (PK): Incremental recovery (IR) at 30 min [ Time Frame: Within 30 mins pre-infusion and post-infusion at 30 minutes ] [ Designated as safety issue: No ]
    IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 30±5 minutes for pre-surgical PK.
  • Presurgical Pharmacokinetics (PK): Elimination phase half-life (T 1/2) [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    T1/2 was determined as ln2 / λz.
  • Presurgical Pharmacokinetics (PK): Volume of distribution at steady state (Vss) [ Time Frame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr ] [ Designated as safety issue: No ]
    Vss was computed as CL·MRT.
  • Incremental recovery (IR) at 15±5 Minutes Following Loading Dose Prior to Surgery [ Time Frame: Within 60 minutes prior to surgery and 15 ± 5 minutes after loading dose/rebolus, if applicable. ] [ Designated as safety issue: No ]
    IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 15±5 minutes for the loading dose.
  • Intraoperative hemostatic efficacy [ Time Frame: At completion of surgery ] [ Designated as safety issue: No ]
    Assessment on a scale of "excellent", "good", "fair" and "none"
  • Actual intraoperative blood loss [ Time Frame: At completion of surgery ] [ Designated as safety issue: No ]
    Actual intraoperative blood loss compared to average and maximum blood loss predicted preoperatively by the operating surgeon
Complete list of historical versions of study NCT01507896 on ClinicalTrials.gov Archive Site
Not Provided
  • Postoperative hemostatic efficacy [ Time Frame: At time of drain removal, if applicable, or approx. 72 hours postoperatively ] [ Designated as safety issue: No ]
    Assessment on a scale of "excellent", "good", "fair" and "none"
  • Actual postoperative blood loss [ Time Frame: At time of drain removal, if applicable, or approx. 72 hours postoperatively ] [ Designated as safety issue: No ]
    Actual postoperative blood loss until drain removal, if applicable, compared to average and maximum blood loss predicted preoperatively by the operating surgeon
  • Development of inhibitory and total binding antibodies to FIX [ Time Frame: 3 years (at study completion) ] [ Designated as safety issue: Yes ]
  • Adverse events related to BAX326 [ Time Frame: 3 years (at study completion) ] [ Designated as safety issue: Yes ]
  • Occurrence of thrombotic events [ Time Frame: 3 years (at study completion) ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
BAX 326 Surgery Study in Hemophilia B Patients
BAX 326 (Recombinant Factor IX): A Phase 3 Prospective, Multicenter Study Evaluating Efficacy and Safety in Previously Treated Patients With Severe (FIX Level < 1%) or Moderately Severe (FIX Level 1-2%) Hemophilia B Undergoing Surgical or Other Invasive Procedures
The purpose of the study is to assess the hemostatic efficacy and safety of BAX 326 in subjects with severe (FIX level < 1%) or moderately severe (FIX level 1-2%) hemophilia B undergoing major or minor elective or emergency surgical, dental or other invasive procedures.
Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia B
Biological: Recombinant factor IX
Following a loading dose with BAX326, participants will receive BAX326 as a bolus infusion. The treatment regimen will be determined by the intensity and duration of the hemostatic challenge and the institution´s standard of care. The dose will be tailored to raise FIX concentration to at least 80%-100% of normal for major surgeries and to at least 30%-60% of normal for minor surgeries.
Other Names:
  • BAX326
  • RIXUBIS
Experimental: BAX326 in Surgery
Intervention: Biological: Recombinant factor IX
Windyga J, Lissitchkov T, Stasyshyn O, Mamonov V, Ghandehari H, Chapman M, Fritsch S, Wong WY, Pavlova BG, Abbuehl BE. Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study. Haemophilia. 2014 Sep;20(5):651-8. doi: 10.1111/hae.12419. Epub 2014 Apr 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
May 2014
May 2014   (final data collection date for primary outcome measure)

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 1-2%) hemophilia B (based on the one stage activated partial thromboplastin time (aPTT) assay), as tested at screening at the central laboratory.
  • Participant requires surgery
  • Participant has previously been treated with plasma-derived and/or recombinant FIX concentrate(s) for a minimum of 150 exposure days
  • Participant has no evidence of a history of FIX inhibitors
  • Participant is immunocompetent as evidenced by a CD4 count ≥ 200 cells/mm3.
  • Participant is human immunodeficiency (HIV) negative or is HIV+ with a viral load < 200 particles/μL ~ < 400,000 copies/mL.

Main Exclusion Criteria:

  • Participant has a history of FIX inhibitors with a titer ≥ 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening.
  • Participant has a detectable FIX inhibitor at screening, with a titer ≥0.6 Bethesda Units (BU) as determined by the Nijmegen modification of the Bethesda assay in the central laboratory.
  • Participant has a history of allergic reaction or evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
  • Known hypersensitivity to hamster proteins or recombinant furin.
  • Evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
  • Abnormal renal function
  • Severe chronic liver disease
  • Active hepatic disease with ALT or AST levels > 5 times the upper limit of normal.
  • Diagnosis of an iherited or acquired hemostatic defect other than hemophilia B.
  • Platelet count < 100,000/mL.
Both
12 Years to 65 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Bulgaria,   Chile,   Colombia,   Czech Republic,   Poland,   Romania,   Russian Federation,   Ukraine,   United Kingdom
Brazil,   Japan,   Sweden
 
NCT01507896
251002, 2011-000413-39
Yes
Not Provided
Not Provided
Baxalta US Inc.
Baxalta US Inc.
Not Provided
Study Director: Baxalta Study Director Baxalta US Inc.
Baxalta US Inc.
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP