Clinical trial NCT01286779: BAX 326 (rFIX) Continuation Study
Official title: BAX 326 (Recombinant Factor IX): Evaluation of Safety, Immunogenicity, and Hemostatic Efficacy in Previously Treated Patients With Severe (FIX Level < 1%) or Moderately Severe (FIX Level <= 2%) Hemophilia B - A Continuation Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 117
Sex: ALL
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 this BAX 326 Continuation Study is to further investigate incremental recovery over time, the hemostatic efficacy, the safety, immunogenicity, and health-related quality of life (HR QoL) of BAX 326 in previously treated patients (PTPs) with severe and moderately severe hemophilia B who participated in BAX 326 pivotal study 250901 or BAX 326 pediatric study 251101.


Eligibility criteria: Main Inclusion Criteria:

* Subject and/or legal representative has/have voluntarily provided signed informed consent
* Subject has completed Baxter clinical study 250901 (pivotal study) or Baxter clinical study 251101 (pediatric study)
* Subject was 12 to 65 years old at the time of screening for Study 250901 or \< 12 years old at the time of screening for Study 251101
* Subject 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
* Subject has not developed an inhibitory FIX antibody during Baxter Pivotal Study 250901 or Pediatric Study 251101

Main Exclusion Criteria:

* Subject received factor IX product(s) other than BAX 326 upon completion of Baxter Pivotal Study 250901 or Pediatric Study 251101
* Subject has been diagnosed with an acquired hemostatic defect other than hemophilia B
* For subjects transferring from Pivotal Study 250901: Subject's weight is \< 35 kg or \> 120 kg
* Subject is planned to take part in any other clinical study, with the exception of BAX 326 Surgery study as described in this protocol, during the course of the Continuation Study

Primary outcomes:
measure: Adverse Events Possibly or Probably Related to the Investigational Product
timeFrame: Assessed (based on patient diary) every 3 months until study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
Secondary outcomes:
measure: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode Required Until Bleed Resolution
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Annualized Bleed Rate During Prophylaxis Treatment
timeFrame: For prophylactic treatment the period from first to last prophylactic infusion is considered.
measure: Consumption of BAX 326: Number of Infusions Per Month and Per Year
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Consumption of BAX 326: Weight Adjusted Consumption Per Month and Per Year
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Consumption of BAX326: Weight Adjusted Consumption Per Bleeding Episode
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Development of Inhibitory and Total Binding Antibodies to Factor IX
timeFrame: Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.
measure: Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin
timeFrame: Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.
measure: Occurrence of Severe Allergic Reactions and Thrombotic Events
timeFrame: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
measure: Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs
timeFrame: Measurements at screening and at study completion/termination are included in the analysis.
measure: Pharmacokinetics: Incremental Recovery (IR) Over Time
timeFrame: IR over time was measured as Baseline and at Completion/Termination visit within 30 minutes pre-infusion and at 30 (± 5) minutes post-infusion.
measure: Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours
measure: Pharmacokinetics: Elimination Phase Half-life (T1/2)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours
measure: Pharmacokinetics: Mean Residence Time (MRT)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours
measure: Pharmacokinetics: Systemic Clearance (CL)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours
measure: Pharmacokinetics: Volume of Distribution at Steady State (Vss)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours
measure: Pharmacokinetics: Incremental Recovery (IR)
timeFrame: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
measure: Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36
timeFrame: Baseline at exposure day 1 and at study completion/termination.
measure: Changes in Health Related Quality of Life Using the Peds QL
timeFrame: Baseline at exposure day 1 and at study completion/termination.
measure: Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire Haemo-QoL and Haem-A-QoL
timeFrame: Baseline at exposure day 1 and at study completion/termination.
measure: Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score.
timeFrame: Baseline at exposure day 1 and at study completion/termination.
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Instituto de Hematología y Medicina Clíncia Rubén Dávoli
city: Sao Paulo
country: Brazil
facility: UNIFESP - Universidade Estadual de Sao Paulo
city: Sofia
country: Bulgaria
facility: Specialized Haematological Hospital "Joan Pavel"
city: Santiago
country: Chile
facility: Hospital Dr. Sotero del Rio
city: Bogotá
country: Colombia
facility: Hospital de San Jose
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Prague
country: Czechia
facility: Klinika detské hematologie a onkologie
city: New Delhi
country: India
facility: Maulana Azad Medical College and Associated Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital, National Center for Hereditary Coagulation Disorders
city: Catania
country: Italy
facility: University Hospital Policlinico Vittorio Emanuele, Hospital Ferrarotto Alessi
city: Florence
country: Italy
facility: University Hospital Careggi, Agency of Hemophilia - Regional Reference Center for Inherited Bleeding
city: Foggia
country: Italy
facility: University of Foggia Riuniti Hospital, Department of Clinical and Experimental Medicine
city: Naples
country: Italy
facility: Hospital San Giovanni Bosco, Center for Hemophilia and Thrombosis, Department of Hematology
city: Padova
country: Italy
facility: Padova University Hospital, Medical Clinic II, Center for Hemophilia
city: Nara
country: Japan
facility: Nara Medical University, Department of Pediatrics
city: Tokyo
country: Japan
facility: Tokyo Medical University
city: Tokyo
country: Japan
facility: Ogikubo Hospital
city: Gdansk
country: Poland
facility: Hematology and Transplantology Clinic, University Clinic Centre - Medical University Hospital
city: Krakow
country: Poland
facility: University Pediatric Hospital in Cracow
city: Krakow
country: Poland
facility: Medical College of the Jagiellonian University, Department of Hematology
city: Lodz
country: Poland
facility: Copernicus Hospital, Medical University in Lodz, Department of Hematology
city: Szczecin
country: Poland
facility: Professor Tadeusz Sokolowski Independent Public Teaching Hospital No. 1 of the Pomeranian Medical University in Szczecin
city: Warsaw
country: Poland
facility: Klinika Hematologii
city: Warsaw
country: Poland
facility: Institute of Haematology and Transfusion Medicine
city: Bucharest
country: Romania
facility: Prof. Dr. C.T. Nicolau National Institute for Transfusional Hematology
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Clinical Children´s Hospital
city: Ekaterinburg
country: Russian Federation
facility: Regional clinical 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: Pediatric Regional Clinical Hospital, Hematology Department
city: Moscow
country: Russian Federation
facility: Hematology Research Center RAMS, Department of Reconstructive Orthopedics for Haemophilia Patients
city: St. Petersburg
country: Russian Federation
facility: Republican Center for Hemophilia Treatment Outpatient Clinic No. 37
city: Malmö
country: Sweden
facility: Malmö University Hospital, Department of Coagulation Disorders
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital
state: Taipei
city: Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Lviv
country: Ukraine
facility: State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine"
city: London
country: United Kingdom
facility: Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Royal Free Hospital
city: Manchester
country: United Kingdom
facility: Manchester Children's Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Windyga J, Stasyshyn O, Lissitchkov T, Mamonov V, Serban M, Rusen L, Ploder B, Tangada S. Safety, Immunogenicity, and Hemostatic Efficacy of Nonacog Gamma in Patients With Severe or Moderately Severe Hemophilia B: A Continuation Study. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620950836. doi: 10.1177/1076029620950836.