Clinical trial NCT01488994: BAX 326 Pediatric Study
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 1-2%) Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-12-09
Enrollment: 23
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Adverse Events (AEs) Possibly or Probably Related to BAX326
timeFrame: Throughout study period (approximately 17 months)
Secondary outcomes:
measure: Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion Per Dose (AUC 0-72h/Dose)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints
measure: Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
measure: Pharmacokinetics (PK): Mean Residence Time (MRT)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
measure: Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
measure: Pharmacokinetics (PK): Incremental Recovery (IR)
timeFrame: Within 30 mins pre-infusion and 30 mins post-infusion
measure: Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
measure: Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
timeFrame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
measure: Pharmacokinetics (PK): Incremental Recovery (IR) Over Time
timeFrame: Within 30 mins pre-infusion and 30 mins post-infusion at baseline, Week 5, Week 13 and Week 26.
measure: Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode
timeFrame: Throughout study period (approximately 17 months)
measure: Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed
timeFrame: Throughout study period (approximately 17 months)
measure: Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR)
timeFrame: Throughout study period (approximately 17 months)
measure: Consumption of BAX326: Number of Infusions Per Month
timeFrame: Throughout study period (approximately 17 months)
measure: Consumption of BAX326: Number of Infusions Per Year
timeFrame: Throughout study period (approximately 17 months)
measure: Consumption of BAX326: Weight-adjusted Consumption Per Month
timeFrame: Throughout study period (approximately 17 months)
measure: Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized)
timeFrame: Throughout study period (approximately 17 months)
measure: Consumption of BAX326: Weight-adjusted Consumption Per Event
timeFrame: Throughout study period (approximately 17 months)
measure: Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
timeFrame: Throughout study period (approximately 17 months)
measure: Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)
timeFrame: Throughout study period (approximately 17 months)
measure: Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis
timeFrame: Throughout study period (approximately 17 months)
measure: Safety: Number of Participants With Thrombotic Events
timeFrame: Throughout study period (approximately 17 months)
measure: Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs
timeFrame: Throughout study period (approximately 17 months)
measure: Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin)
timeFrame: Throughout study period (approximately 17 months)
measure: Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score
timeFrame: Baseline and 6 months
measure: Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score
timeFrame: Baseline and 6 months
measure: Health Resource Use: Number of Hospitalizations
timeFrame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
measure: Health Resource Use: Length of Hospitalization
timeFrame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
measure: Health Resource Use: Unscheduled Doctor's Office Visits
timeFrame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
measure: Health Resource Use: Emergency Room Visits
timeFrame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
measure: Health Resource Use: Days Lost From School
timeFrame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Other outcomes:
Locations:
city: New Delhi
country: India
facility: LNJP Maulana Azad Medical College & Associated Hospitals
city: Krakow
country: Poland
facility: University Pediatric Hospital
city: Olsztyn
country: Poland
facility: Stanislaw Popowski Provincial Specialist Pediatric Hospital
city: Szczecin
country: Poland
facility: Professor Tadeusz Sokolowski Independent Public Teaching Hospital of the Pomeranian Medical University in Szczecin
city: Bucharest
country: Romania
facility: S.C. Sanador SRL
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Children's Hospital
city: Ekaterinburg
country: Russian Federation
facility: Regional Clinical Hospital
city: Krasnodar
country: Russian Federation
facility: Pediatric Regional Clinical Hospital, Hematology Department
city: St. Petersburg
country: Russian Federation
facility: Republican Center for Hemophilia Treatment
city: Lviv
country: Ukraine
facility: State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine"
city: Manchester
country: United Kingdom
facility: Manchester Children´s Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Urasinski T, Stasyshyn O, Andreeva T, Rusen L, Perina FG, Oh MS, Chapman M, Pavlova BG, Valenta-Singer B, Abbuehl BE. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial. Haemophilia. 2015 Mar;21(2):196-203. doi: 10.1111/hae.12548. Epub 2014 Dec 11.