BAX 326 Surgery Study in Hemophilia B Patients

Baxalta now part of Shire30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia B

Interventions

Recombinant factor IXBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (14)

Instituto de Hematología y Medicina Clínica Rubén Dávoli

Rosario, Argentina

Specialized Haematological Hospital "Joan Pavel"

Sofia, Bulgaria

Outcomes

Primary Outcomes

Intraoperative Hemostatic Efficacy

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

Time frame: On day of surgery

Actual Intraoperative Blood Loss

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.

Time frame: On day of surgery

Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon

Predicted average/maximum blood loss minus actual blood loss. Prior to the surgery, the surgeon predicted the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study participant for the intraoperative period.

Time frame: On day of surgery

Postoperative Hemostatic Efficacy at Drain Removal

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Hospital Dr. Sotero del Rio

Santiago, Chile

Centro Medico Imbanaco

Cali, Colombia

Klinika detska hematologie a onkologie, Fakultni Nemocnice Motol

Prague, Czechia

Medical University Lodz, Copernicus Hospital, Department of Hematology

Lodz, Poland

Independent Public Pediatric Teaching Hospital, Clinical Department of Hematology and Pediatrics

Warsaw, Poland

Institute of Haematology and Transfusion Medicine

Warsaw, Poland

Louis Turcanu Emergency Clinical Children´s Hospital

Timișoara, Romania

Federal State Institution Kirov, Hematology and Blood Transfusion Research Institute under the Federal Agency for High-Tech Medical Care

Kirov, Russia

...and 4 more locations

Time frame: At drain removal (from 1-3 days postoperatively)

Postoperative Hemostatic Efficacy at Postoperative Day 3

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

Time frame: At postoperative day 3 (approximately 72 hours postoperatively)

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)

Actual Postoperative Blood Loss

Postoperative blood loss was based on the drainage fluid and was only assessed for participants who had a drain placed during surgery.

Time frame: At drain removal (from 1-3 days postoperatively)

Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon

Predicted average/maximum blood loss minus actual blood loss for participants who had a drain placed during surgery. Prior to the surgery, the surgeon will predict the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study subject for the postoperative period until drain removal.

Time frame: At postoperative day 3 (approximately 72 hours postoperatively)

Daily Weight-Adjusted Dose of BAX326 Per Participant

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.

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)

Total Weight-Adjusted Dose of BAX326 Per Participant

Assessed for the intra- and postoperative periods.

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)

Number of Units of Blood Product Transfused

Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.

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)

Volume of Blood Product Transfused

Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.

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)

Safety: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)

Time frame: Throughout the study period (approximately 2 years 5 months)

Safety: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)

If there was more than 2-dilution increase as compared to pre-study level at screening.

Time frame: Throughout the study period (approximately 2 years 5 months)

Safety: Number of Adverse Events Related to BAX326

Time frame: Throughout the study period (approximately 2 years 5 months)

Safety: Occurence of a Thrombotic Event

Time frame: Throughout the study period (approximately 2 years 5 months)

Pre-Surgical Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 72 Hours Post-infusion Per Dose

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.