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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
All participants underwent a pharmacokinetic evaluation with BAX326 (recombinant Factor IX) followed by twice weekly prophylactic treatment for 6 months or for at least 50 exposure days, whichever occurred last.
LNJP Maulana Azad Medical College & Associated Hospitals
New Delhi, India
University Pediatric Hospital
Krakow, Poland
Stanislaw Popowski Provincial Specialist Pediatric Hospital
Olsztyn, Poland
Adverse Events (AEs) Possibly or Probably Related to BAX326
Time frame: Throughout study period (approximately 17 months)
Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion Per Dose (AUC 0-72h/Dose)
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints
Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose)
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Pharmacokinetics (PK): Mean Residence Time (MRT)
Computed as total area under the first moment curve (total AUMC) divided by the total area under the concentration versus time curve (total AUC)
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL)
Computed as the dose divided by total Area under the curve (AUC)
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Pharmacokinetics (PK): Incremental Recovery (IR)
The rise in FIX activity in IU/dL per unit dose administered in IU/kg. Calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose
Time frame: Within 30 mins pre-infusion and 30 mins post-infusion
Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)
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Professor Tadeusz Sokolowski Independent Public Teaching Hospital of the Pomeranian Medical University in Szczecin
Szczecin, Poland
S.C. Sanador SRL
Bucharest, Romania
Louis Turcanu Emergency Children's Hospital
Timișoara, Romania
Pediatric Regional Clinical Hospital, Hematology Department
Krasnodar, Russia
Republican Center for Hemophilia Treatment
Saint Petersburg, Russia
Regional Clinical Hospital
Yekaterinburg, Russia
State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine"
Lviv, Ukraine
...and 1 more locations
Calculated as log\_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
Computed as Clearance (CL) \* Mean residence time (MRT)
Time frame: Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Pharmacokinetics (PK): Incremental Recovery (IR) Over Time
IR calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose. IR is determined at baseline (PK analysis), Week 5, Week 13 and Week 26 timepoints. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \> 6 years of age; pediatric participants 6 to \<12 years of age; pharmacokinetic Full Analysis Set (PKFAS).
Time frame: Within 30 mins pre-infusion and 30 mins post-infusion at baseline, Week 5, Week 13 and Week 26.
Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode
Time frame: Throughout study period (approximately 17 months)
Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed
Rating Scale for Treatment of bleeding episodes (4-point ordinal scale): - Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. - Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. - Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. - None: No improvement or condition worsens.
Time frame: Throughout study period (approximately 17 months)
Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR)
The annualized bleeding rate (ABR) during prophylaxis was calculated only for participants who had adequate treatment time for bleeding rate assessment (i.e., more than 3 months of prophylaxis treatment). The observation period for prophylaxis was to be the time between the first and the last prophylactic infusions. The treatment period for surgery was to be excluded from the bleed rate calculation. ABR calculated as (Number of bleeding episodes/observed treatment period in days) \* 365.25.
Time frame: Throughout study period (approximately 17 months)
Consumption of BAX326: Number of Infusions Per Month
Time frame: Throughout study period (approximately 17 months)
Consumption of BAX326: Number of Infusions Per Year
Time frame: Throughout study period (approximately 17 months)
Consumption of BAX326: Weight-adjusted Consumption Per Month
Time frame: Throughout study period (approximately 17 months)
Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized)
Time frame: Throughout study period (approximately 17 months)
Consumption of BAX326: Weight-adjusted Consumption Per Event
Event includes prophylactic infusions of study product and infusions of study product for treatment of bleeding episodes (BEs).
Time frame: Throughout study period (approximately 17 months)
Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
Time frame: Throughout study period (approximately 17 months)
Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)
If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay. AB=antibodies in category for outcome measure data.
Time frame: Throughout study period (approximately 17 months)
Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis
Time frame: Throughout study period (approximately 17 months)
Safety: Number of Participants With Thrombotic Events
Time frame: Throughout study period (approximately 17 months)
Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs
Categories consist of Clinically Significant (CS) changes in haemaotology parameters, clinical chemistry parameters and vital signs. Abbreviations in categories; Clin=clinical; params=parameters
Time frame: Throughout study period (approximately 17 months)
Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin)
If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay.
Time frame: Throughout study period (approximately 17 months)
Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score
For this study, the PedsQL™ questionnaires for participants 2 to 7 years of age (parent-proxy versions for age groups 2-4 years and 5-7 years) and PedsQL™ Child version for participants 8 to 12 years of age were used. The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. A 5-point score is used for each domain: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0 so that higher scores indicate better quality of life (QoL). The total score is the mean (average) of all scores from the 4 domains. The change from baseline in total score is reported- a positive score indicates a better QoL compared to baseline and a negative score indicates a poorer QoL compared to baseline.
Time frame: Baseline and 6 months
Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score
The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.
Time frame: Baseline and 6 months
Health Resource Use: Number of Hospitalizations
The number of hospitalizations per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \< 6 years of age; pediatric participants 6 to \<12 years of age; Full Analysis Set.
Time frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Health Resource Use: Length of Hospitalization
The length of hospitalization per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \< 6 years of age; pediatric participants 6 to \<12 years of age; Full Analysis Set.
Time frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Health Resource Use: Unscheduled Doctor's Office Visits
The number of unscheduled doctor's Office visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \< 6 years of age; pediatric participants 6 to \<12 years of age; Full Analysis Set.
Time frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Health Resource Use: Emergency Room Visits
The number of Emergency Room visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \< 6 years of age; pediatric participants 6 to \<12 years of age; Full Analysis Set.
Time frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Health Resource Use: Days Lost From School
The number of days lost from school per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants \< 6 years of age; pediatric participants 6 to \<12 years of age; Full Analysis Set.
Time frame: Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26