Clinical trial NCT01507896: BAX 326 Surgery Study in Hemophilia B Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-01-11
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 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.

Primary outcomes:
measure: Intraoperative Hemostatic Efficacy
timeFrame: On day of surgery
measure: Actual Intraoperative Blood Loss
timeFrame: On day of surgery
measure: Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon
timeFrame: On day of surgery
measure: Postoperative Hemostatic Efficacy at Drain Removal
timeFrame: At drain removal (from 1-3 days postoperatively)
measure: Postoperative Hemostatic Efficacy at Postoperative Day 3
timeFrame: At postoperative day 3 (approximately 72 hours postoperatively)
measure: Postoperative Hemostatic Efficacy on Day of Discharge
timeFrame: At discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)
measure: Actual Postoperative Blood Loss
timeFrame: At drain removal (from 1-3 days postoperatively)
measure: Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon
timeFrame: At postoperative day 3 (approximately 72 hours postoperatively)
measure: Daily Weight-Adjusted Dose of BAX326 Per Participant
timeFrame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)
measure: Total Weight-Adjusted Dose of BAX326 Per Participant
timeFrame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)
measure: Number of Units of Blood Product Transfused
timeFrame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)
measure: Volume of Blood Product Transfused
timeFrame: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)
measure: Safety: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
timeFrame: Throughout the study period (approximately 2 years 5 months)
measure: Safety: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)
timeFrame: Throughout the study period (approximately 2 years 5 months)
measure: Safety: Number of Adverse Events Related to BAX326
timeFrame: Throughout the study period (approximately 2 years 5 months)
measure: Safety: Occurence of a Thrombotic Event
timeFrame: Throughout the study period (approximately 2 years 5 months)
measure: Pre-Surgical Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 72 Hours Post-infusion Per Dose
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Pre-Surgical Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve Per Dose (Total AUC/Dose)
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Pre-Surgical Pharmacokinetics (PK): Mean Residence Time (MRT)
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Pre-Surgical Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL)
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Pre-Surgical Pharmacokinetics (PK): Incremental Recovery (IR) at 30 Min
timeFrame: Within 30 mins pre-infusion and post-infusion at 30 minutes
measure: Pre-Surgical Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Pre-Surgical Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
timeFrame: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr
measure: Incremental Recovery (IR) at 15±5 Minutes Following Loading Dose Prior to Surgery
timeFrame: Within 60 minutes prior to surgery and 15 ± 5 minutes after loading dose/rebolus, if applicable.
Secondary outcomes:
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Instituto de Hematología y Medicina Clínica Rubén Dávoli
city: Sofia
country: Bulgaria
facility: Specialized Haematological Hospital "Joan Pavel"
city: Santiago
country: Chile
facility: Hospital Dr. Sotero del Rio
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
city: Prague
country: Czechia
facility: Klinika detska hematologie a onkologie, Fakultni Nemocnice Motol
city: Lodz
country: Poland
facility: Medical University Lodz, Copernicus Hospital, Department of Hematology
city: Warsaw
country: Poland
facility: Independent Public Pediatric Teaching Hospital, Clinical Department of Hematology and Pediatrics
city: Warsaw
country: Poland
facility: Institute of Haematology and Transfusion Medicine
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Clinical Children´s Hospital
city: Kirov
country: Russian Federation
facility: Federal State Institution Kirov, Hematology and Blood Transfusion Research Institute under the Federal Agency for High-Tech Medical Care
city: Krasnodar
country: Russian Federation
facility: Children's Territorial Clinical Hospital
city: Moscow
country: Russian Federation
facility: Hematology Research Center RAMS
city: Lviv
country: Ukraine
facility: State Institution "Institute of Blood Pathology and Transfusion Medicine under the Academy of Medical Sciences of Ukraine"
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital, Department of Hematology
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Windyga J, Timofeeva M, Stasyshyn O, Mamonov V, Lamas Castellanos JL, Lissitchkov T, Chojnowski K, Chapman M, Pavlova BG, Tangada S. Phase 3 Clinical Trial: Perioperative Use of Nonacog Gamma, a Recombinant Factor IX, in Previously Treated Patients With Moderate/Severe Hemophilia B. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620946839. doi: 10.1177/1076029620946839.