Hemophilia B
Conditions
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.
Interventions
BIOLOGICALBAX326
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.
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events (AEs) Possibly or Probably Related to BAX326 | Throughout study period (approximately 17 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose) | Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. | — |
| Pharmacokinetics (PK): Mean Residence Time (MRT) | Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. | Computed as total area under the first moment curve (total AUMC) divided by the total area under the concentration versus time curve (total AUC) |
| Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. | Computed as the dose divided by total Area under the curve (AUC) |
| Pharmacokinetics (PK): Incremental Recovery (IR) | Within 30 mins pre-infusion and 30 mins post-infusion | 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 |
| Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. | Calculated as log\_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model |
| Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details. | Computed as Clearance (CL) \* Mean residence time (MRT) |
| Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Within 30 mins pre-infusion and 30 mins post-infusion at baseline, Week 5, Week 13 and Week 26. | 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). |
| Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Throughout study period (approximately 17 months) | — |
| Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Throughout study period (approximately 17 months) | 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. |
| Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR) | Throughout study period (approximately 17 months) | 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. |
| Consumption of BAX326: Number of Infusions Per Month | Throughout study period (approximately 17 months) | — |
| Consumption of BAX326: Number of Infusions Per Year | Throughout study period (approximately 17 months) | — |
| Consumption of BAX326: Weight-adjusted Consumption Per Month | Throughout study period (approximately 17 months) | — |
| Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized) | 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) | Within 30 mins pre-infusion and 4 post-infusion timepoints | — |
| Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | Throughout study period (approximately 17 months) | — |
| Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | Throughout study period (approximately 17 months) | 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. |
| Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis | Throughout study period (approximately 17 months) | — |
| Safety: Number of Participants With Thrombotic Events | 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 | Throughout study period (approximately 17 months) | Categories consist of Clinically Significant (CS) changes in haemaotology parameters, clinical chemistry parameters and vital signs. Abbreviations in categories; Clin=clinical; params=parameters |
| Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Throughout study period (approximately 17 months) | If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay. |
| Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score | Baseline and 6 months | 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. |
| Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score | Baseline and 6 months | 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. |
| Health Resource Use: Number of Hospitalizations | Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 | 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. |
| Health Resource Use: Length of Hospitalization | Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 | 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. |
| Health Resource Use: Unscheduled Doctor's Office Visits | Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 | 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. |
| Health Resource Use: Emergency Room Visits | Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 | 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. |
| Health Resource Use: Days Lost From School | Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26 | 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. |
| Consumption of BAX326: Weight-adjusted Consumption Per Event | Throughout study period (approximately 17 months) | Event includes prophylactic infusions of study product and infusions of study product for treatment of bleeding episodes (BEs). |
Countries
India, Poland, Romania, Russia, Ukraine, United Kingdom
Participant flow
Recruitment details
Enrollment was conducted at 11 clinical sites in 6 countries (United Kingdom, Poland, Romania, Russian Federation, Ukraine, India). A total of 23 participants were enrolled in the study. Of these, 11 were \< 6 years of age and 12 were 6 to \<12 years of age.
Participants by arm
| Arm | Count |
|---|---|
| Pediatric Participants < 6 Years of Age Pediatric participants \< 6 years of age. All pediatric participants underwent pharmacokinetic (PK) assessment followed by prophylactic treatment with the study product. All participants received the same dosing schedule of study product during the study. After a washout period of 5-7 days, participants received an initial infusion of study product at a dose of 75±5 IU/kg for the PK assessment. For the prophylactic regimen, participants were treated with the recommended dose of 50 IU/kg of study product twice weekly ranging from 40-80 IU/kg for 26±1 weeks or for at least 50 EDs to study product, whichever occurred last. | 11 |
| Pediatric Participants 6 to <12 Years of Age Pediatric participants 6 to \<12 years of age. All pediatric participants underwent pharmacokinetic (PK) assessment followed by prophylactic treatment with the study product. All participants received the same dosing schedule of study product during the study. After a washout period of 5-7 days, participants received an initial infusion of study product at a dose of 75±5 IU/kg for the PK assessment. For the prophylactic regimen, participants were treated with the recommended dose of 50 IU/kg of study product twice weekly ranging from 40-80 IU/kg for 26±1 weeks or for at least 50 EDs to study product, whichever occurred last. | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Pediatric Participants < 6 Years of Age | Pediatric Participants 6 to <12 Years of Age | Total |
|---|---|---|---|
| Age, Continuous | 3.83 years | 9.8 years | 6.94 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 23 |
| serious Total, serious adverse events | 3 / 23 |
Outcome results
Primary
Adverse Events (AEs) Possibly or Probably Related to BAX326
Time frame: Throughout study period (approximately 17 months)
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants < 6 Years of Age | Adverse Events (AEs) Possibly or Probably Related to BAX326 | 0 AEs considered related to BAX326 |
| Pediatric Participants 6 to < 12 Years of Age | Adverse Events (AEs) Possibly or Probably Related to BAX326 | 0 AEs considered related to BAX326 |
| Full Analysis Set | Adverse Events (AEs) Possibly or Probably Related to BAX326 | 0 AEs considered related to BAX326 |
Secondary
Consumption of BAX326: Number of Infusions Per Month
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Number of Infusions Per Month | 6.8 Infusions per month | Standard Deviation 0.44 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Number of Infusions Per Month | 7.2 Infusions per month | Standard Deviation 0.4 |
| Full Analysis Set | Consumption of BAX326: Number of Infusions Per Month | 7.0 Infusions per month | Standard Deviation 0.44 |
Secondary
Consumption of BAX326: Number of Infusions Per Year
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Number of Infusions Per Year | 82.1 Infusions per year | Standard Deviation 5.27 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Number of Infusions Per Year | 85.9 Infusions per year | Standard Deviation 4.79 |
| Full Analysis Set | Consumption of BAX326: Number of Infusions Per Year | 84.1 Infusions per year | Standard Deviation 5.27 |
Secondary
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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for prophylactic infusions | 56.3 IU/kg | Standard Deviation 10.29 |
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for infusions to treat BEs | 57.6 IU/kg | Standard Deviation 11.87 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for prophylactic infusions | 56.2 IU/kg | Standard Deviation 6.55 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for infusions to treat BEs | 62.1 IU/kg | Standard Deviation 16 |
| Full Analysis Set | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for prophylactic infusions | 56.2 IU/kg | Standard Deviation 8.34 |
| Full Analysis Set | Consumption of BAX326: Weight-adjusted Consumption Per Event | Consumption of BAX326 for infusions to treat BEs | 59.9 IU/kg | Standard Deviation 13.74 |
Secondary
Consumption of BAX326: Weight-adjusted Consumption Per Month
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Month | 393.4 IU/kg per month | Standard Deviation 50.53 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Month | 414.8 IU/kg per month | Standard Deviation 58.44 |
| Full Analysis Set | Consumption of BAX326: Weight-adjusted Consumption Per Month | 404.6 IU/kg per month | Standard Deviation 54.66 |
Secondary
Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized)
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized) | 4720.9 IU/kg per year | Standard Deviation 606.31 |
| Pediatric Participants 6 to < 12 Years of Age | Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized) | 4978.2 IU/kg per year | Standard Deviation 701.26 |
| Full Analysis Set | Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized) | 4855.1 IU/kg per year | Standard Deviation 655.93 |
Secondary
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
Population: Participants in the Full Analysis Set who had Haemo-QoL data for baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score | -0.18 Scores on a scale | Standard Deviation 0.456 |
Secondary
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
Population: Participants in the Full Analysis Set who had PedsQL™ data for baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score | Peds-QL 2-4 (N=4) | 3.27 Scores on a scale | Standard Deviation 10.119 |
| Pediatric Participants < 6 Years of Age | Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score | Peds-QL 5-7 (N=2) | -7.07 Scores on a scale | Standard Deviation 6.917 |
| Pediatric Participants < 6 Years of Age | Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score | Peds-QL 8-12 (N=10) | 4.02 Scores on a scale | Standard Deviation 11.038 |
Secondary
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
Population: Participants who missed days from school
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health Resource Use: Days Lost From School | PK assessment (N=11, 12, 23) | 0.0 Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Days Lost From School | Week 5 (N=11, 12, 23) | 0.0 Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Days Lost From School | Week 13 (N=11, 11, 22) | 0.0 Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Days Lost From School | Week 26 (N=11, 11, 22) | 0.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Days Lost From School | Week 26 (N=11, 11, 22) | 0.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Days Lost From School | PK assessment (N=11, 12, 23) | 0.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Days Lost From School | Week 13 (N=11, 11, 22) | 0.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Days Lost From School | Week 5 (N=11, 12, 23) | 0.0 Days |
| Full Analysis Set | Health Resource Use: Days Lost From School | Week 26 (N=11, 11, 22) | 0.0 Days |
| Full Analysis Set | Health Resource Use: Days Lost From School | Week 5 (N=11, 12, 23) | 0.0 Days |
| Full Analysis Set | Health Resource Use: Days Lost From School | Week 13 (N=11, 11, 22) | 0.0 Days |
| Full Analysis Set | Health Resource Use: Days Lost From School | PK assessment (N=11, 12, 23) | 0.0 Days |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health Resource Use: Emergency Room Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Emergency Room Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Emergency Room Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Emergency Room Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Emergency Room Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Emergency Room Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Emergency Room Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Emergency Room Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Emergency Room Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Emergency Room Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Emergency Room Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Emergency Room Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health Resource Use: Length of Hospitalization | PK assessment | NA Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Length of Hospitalization | Week 5 | NA Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Length of Hospitalization | Week 13 (N=1, 1, 2) | 2.0 Days |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Length of Hospitalization | Week 26 (N=NA, 1, 1) | NA Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Length of Hospitalization | Week 26 (N=NA, 1, 1) | 13.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Length of Hospitalization | PK assessment | NA Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Length of Hospitalization | Week 13 (N=1, 1, 2) | 4.0 Days |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Length of Hospitalization | Week 5 | NA Days |
| Full Analysis Set | Health Resource Use: Length of Hospitalization | Week 26 (N=NA, 1, 1) | 13.0 Days |
| Full Analysis Set | Health Resource Use: Length of Hospitalization | Week 5 | NA Days |
| Full Analysis Set | Health Resource Use: Length of Hospitalization | Week 13 (N=1, 1, 2) | 3.0 Days |
| Full Analysis Set | Health Resource Use: Length of Hospitalization | PK assessment | NA Days |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health Resource Use: Number of Hospitalizations | Week 26 (N=11, 11, 22) | 0.0 Hospitalizations |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Number of Hospitalizations | Week 13 (N=11, 11, 22) | 0.0 Hospitalizations |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Number of Hospitalizations | Week 5 (N=11, 12, 23) | 0.0 Hospitalizations |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Number of Hospitalizations | Week 26 (N=11, 11, 22) | 0.0 Hospitalizations |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Number of Hospitalizations | Week 5 (N=11, 12, 23) | 0.0 Hospitalizations |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Number of Hospitalizations | Week 13 (N=11, 11, 22) | 0.0 Hospitalizations |
| Full Analysis Set | Health Resource Use: Number of Hospitalizations | Week 13 (N=11, 11, 22) | 0.0 Hospitalizations |
| Full Analysis Set | Health Resource Use: Number of Hospitalizations | Week 5 (N=11, 12, 23) | 0.0 Hospitalizations |
| Full Analysis Set | Health Resource Use: Number of Hospitalizations | Week 26 (N=11, 11, 22) | 0.0 Hospitalizations |
Secondary
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
Population: Participants who had unscheduled visits to a doctor's office
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants < 6 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Pediatric Participants 6 to < 12 Years of Age | Health Resource Use: Unscheduled Doctor's Office Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Unscheduled Doctor's Office Visits | Week 26 (N=11, 11, 22) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Unscheduled Doctor's Office Visits | Week 5 (N=11, 12, 23) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Unscheduled Doctor's Office Visits | Week 13 (N=11, 11, 22) | 0.0 Visits |
| Full Analysis Set | Health Resource Use: Unscheduled Doctor's Office Visits | PK assessment (N=11, 12, 23) | 0.0 Visits |
Secondary
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR) | 1.9 Bleeding episodes per year | Standard Deviation 1.89 |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR) | 3.4 Bleeding episodes per year | Standard Deviation 3.93 |
| Full Analysis Set | Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR) | 2.7 Bleeding episodes per year | Standard Deviation 3.14 |
Secondary
Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode
Time frame: Throughout study period (approximately 17 months)
Population: Participants in the Full Analysis Set who had bleeding episodes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 2 infusions | 1 Bleeding Episodes |
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 1 infusion | 9 Bleeding Episodes |
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding episodes controlled with ≥ 3 infusions | 1 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 2 infusions | 7 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 1 infusion | 6 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding episodes controlled with ≥ 3 infusions | 2 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 1 infusion | 15 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding episodes controlled with ≥ 3 infusions | 3 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode | Bleeding Episodes controlled with 2 infusions | 8 Bleeding Episodes |
Secondary
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)
Population: Participants in the Full Analysis Set who had bleeding episodes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Excellent | 9 Bleeding Episodes |
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Good | 2 Bleeding Episodes |
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Fair | 0 Bleeding Episodes |
| Pediatric Participants < 6 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | None | 0 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | None | 0 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Excellent | 4 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Fair | 1 Bleeding Episodes |
| Pediatric Participants 6 to < 12 Years of Age | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Good | 10 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | None | 0 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Good | 12 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Fair | 1 Bleeding Episodes |
| Full Analysis Set | Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Excellent | 13 Bleeding Episodes |
Secondary
Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)
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.
Population: All participants randomized to 2 groups: Group 1 - BAX326 infusion in the morning PK timepoints: Pre-infusion and post-infusion at 15-30 minutes, then 7, 28 and 52 hours Group 2 - BAX326 infusion in the afternoon PK timepoints: Pre-infusion and post-infusion of 15-30 minutes, then 4, 24 and 69 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | 27.67 hours (hr) | Standard Deviation 2.658 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | 23.15 hours (hr) | Standard Deviation 1.582 |
| Full Analysis Set | Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | 25.31 hours (hr) | Standard Deviation 3.13 |
Secondary
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.
Population: All participants randomized to 2 groups: Group 1 - BAX326 infusion in the morning PK timepoints: Pre-infusion and post-infusion at 15-30 minutes, then 7, 28 and 52 hours Group 2 - BAX326 infusion in the afternoon PK timepoints: Pre-infusion and post-infusion of 15-30 minutes, then 4, 24 and 69 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | 0.1058 dL/(kg*hr) | Standard Deviation 0.0165 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | 0.0874 dL/(kg*hr) | Standard Deviation 0.01213 |
| Full Analysis Set | Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | 0.0962 dL/(kg*hr) | Standard Deviation 0.01689 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) | 0.586 IU/dL : IU/kg | Standard Deviation 0.132 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) | 0.731 IU/dL : IU/kg | Standard Deviation 0.1615 |
| Full Analysis Set | Pharmacokinetics (PK): Incremental Recovery (IR) | 0.665 IU/dL : IU/kg | Standard Deviation 0.1632 |
Secondary
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Baseline (N=10, 12, 22) | 0.586 IU/dL : IU/kg | Standard Deviation 0.132 |
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 5 (N=11, 12, 23) | 0.630 IU/dL : IU/kg | Standard Deviation 0.1028 |
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 13 (N=10, 11, 21) | 0.676 IU/dL : IU/kg | Standard Deviation 0.1211 |
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 26 (N=10, 11, 21) | 0.647 IU/dL : IU/kg | Standard Deviation 0.1274 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 26 (N=10, 11, 21) | 0.795 IU/dL : IU/kg | Standard Deviation 0.1445 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Baseline (N=10, 12, 22) | 0.731 IU/dL : IU/kg | Standard Deviation 0.1615 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 13 (N=10, 11, 21) | 0.733 IU/dL : IU/kg | Standard Deviation 0.14 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 5 (N=11, 12, 23) | 0.726 IU/dL : IU/kg | Standard Deviation 0.1291 |
| Full Analysis Set | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 26 (N=10, 11, 21) | 0.724 IU/dL : IU/kg | Standard Deviation 0.1533 |
| Full Analysis Set | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 5 (N=11, 12, 23) | 0.680 IU/dL : IU/kg | Standard Deviation 0.1245 |
| Full Analysis Set | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Week 13 (N=10, 11, 21) | 0.706 IU/dL : IU/kg | Standard Deviation 0.1313 |
| Full Analysis Set | Pharmacokinetics (PK): Incremental Recovery (IR) Over Time | Baseline (N=10, 12, 22) | 0.665 IU/dL : IU/kg | Standard Deviation 0.1632 |
Secondary
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.
Population: All participants randomized to 2 groups: Group 1 - BAX326 infusion in the morning PK timepoints: Pre-infusion and post-infusion at 15-30 minutes, then 7, 28 and 52 hours Group 2 - BAX326 infusion in the afternoon PK timepoints: Pre-infusion and post-infusion of 15-30 minutes, then 4, 24 and 69 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Mean Residence Time (MRT) | 30.62 hours (hr) | Standard Deviation 3.266 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Mean Residence Time (MRT) | 25.31 hours (hr) | Standard Deviation 1.83 |
| Full Analysis Set | Pharmacokinetics (PK): Mean Residence Time (MRT) | 27.85 hours (hr) | Standard Deviation 3.726 |
Secondary
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
Population: On completion of the study, prospective changes to the planned statistical analysis were made not to analyze AUC 0-72h due to the different time points for the last PK blood sample. Only total AUC \[i.e. AUC 0-infinity\] was included in the PK analysis.
Secondary
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.
Population: All participants randomized to 2 groups: Group 1 - BAX326 infusion in the morning PK timepoints: Pre-infusion and post-infusion at 15-30 minutes, then 7, 28 and 52 hours Group 2 - BAX326 infusion in the afternoon PK timepoints: Pre-infusion and post-infusion of 15-30 minutes, then 4, 24 and 69 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose) | 723.7 IU*hour (hr)/dL | Standard Deviation 119 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose) | 886 IU*hour (hr)/dL | Standard Deviation 133.66 |
| Full Analysis Set | Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose) | 808.4 IU*hour (hr)/dL | Standard Deviation 149.14 |
Secondary
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.
Population: All participants randomized to 2 groups: Group 1 - BAX326 infusion in the morning PK timepoints: Pre-infusion and post-infusion at 15-30 minutes, then 7, 28 and 52 hours Group 2 - BAX326 infusion in the afternoon PK timepoints: Pre-infusion and post-infusion of 15-30 minutes, then 4, 24 and 69 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | 3.225 dL/kg | Standard Deviation 0.5233 |
| Pediatric Participants 6 to < 12 Years of Age | Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | 2.209 dL/kg | Standard Deviation 0.3165 |
| Full Analysis Set | Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | 2.695 dL/kg | Standard Deviation 0.6662 |
Secondary
Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | 0 Participants |
| Full Analysis Set | Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | 0 Participants |
Secondary
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | 0 Participants |
| Full Analysis Set | Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | 0 Participants |
Secondary
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to CHO proteins | 0 Participants |
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to rFurin | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to CHO proteins | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to rFurin | 0 Participants |
| Full Analysis Set | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to CHO proteins | 0 Participants |
| Full Analysis Set | Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin) | Number who developed antibodies to rFurin | 0 Participants |
Secondary
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in vital signs | 0 Participants |
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in clin. chemistry params | 0 Participants |
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in haematology params | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in vital signs | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in haematology params | 2 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in clin. chemistry params | 0 Participants |
| Full Analysis Set | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in vital signs | 0 Participants |
| Full Analysis Set | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in clin. chemistry params | 0 Participants |
| Full Analysis Set | Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs | Number with CS changes in haematology params | 2 Participants |
Secondary
Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis | 0 Participants |
| Full Analysis Set | Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis | 0 Participants |
Secondary
Safety: Number of Participants With Thrombotic Events
Time frame: Throughout study period (approximately 17 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants < 6 Years of Age | Safety: Number of Participants With Thrombotic Events | 0 Participants |
| Pediatric Participants 6 to < 12 Years of Age | Safety: Number of Participants With Thrombotic Events | 0 Participants |
| Full Analysis Set | Safety: Number of Participants With Thrombotic Events | 0 Participants |