Hemophilia B
Conditions
Brief summary
The purpose of this pivotal Phase 1/3 study is to determine the pharmacokinetic (PK) parameters, the hemostatic efficacy, and the safety of BAX 326, a recombinant factor IX, in previously treated patients (PTPs) with severe and moderately severe hemophilia B.
Interventions
BIOLOGICALBAX 326
* Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX * Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only * Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1
BIOLOGICALBeneFIX
* Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX. * BeneFIX only used in Part 1 of this study. * Study Part 2 and 3 only utilized BAX326
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Participant is 12 to 65 years old at the time of screening * Participant and/or legal representative has/have provided signed informed consent * Participant has severe (factor IX (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 is previously treated with plasma-derived or recombinant FIX concentrate(s) for a minimum of 150 exposure days (EDs) (based on the participant's medical records); if a verifiable, documented history is unavailable, the participant can be enrolled if s/he has 100-150 EDs to any FIX product that are not fully documented and has participated in Study 050901 for at least 50 EDs to Immunine prior to enrollment (not valid for US and Japan). * Participant has no evidence of a history of FIX inhibitors * If the participant is to receive prophylactic treatment, the participant is willing to receive prophylactic treatment over a period of 6 months. * If the participant is to receive on-demand treatment, the participant has ≥12 documented bleeding episodes requiring treatment within 12 months prior to enrollment and is willing to receive on-demand treatment for the duration of this study. Main
Exclusion criteria
* The 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 * The participant has a detectable FIX inhibitor at screening, with a titer ≥0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory * The participant's weight is \< 35 kg or \> 120 kg * The participant has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s) * The participant has a known hypersensitivity to hamster proteins or recombinant furin (rFurin) * The participant has ongoing or recent evidence of a thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose | 72 hours | Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Parts 1 and 3: Mean Residence Time (MRT) | 0-30 minutes before infusion up to 72 hours post-infusion | Computed as Area under the moment curve 0-∞ (AUMC0-∞) / AUC0-∞- TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration \[hr\] The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Study Parts 1 and 3: Clearance (CL) | 0-30 minutes before infusion up to 72 hours post-infusion | Computed as Dose/ AUC0-∞. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax) | 0-30 minutes before infusion up to 1 hour post-infusion | Defined as (Cmax - Cpre-infusion)/Dose, where maximum concentration (Cmax) will be determined as the highest concentration achieved within one hour after infusion. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Incremental Recovery (IR) at 30 Minutes Over Time | 0-30 minutes before infusion and 30 minutes post-infusion | IR at 30 Minutes was measured at the following time points during the study: - Part 1 or Part 2, Exposure Day (ED) 1. (If participant was present for Study Part 1, then ED 1 from Part 1 was used. If Participant entered study in Study Part 2, then ED 1 from Part 2 was used.) - Part 2: Week 5 - Part 2: Week 13 - Part 2 or Part 3: Week 26 (Week 26 of study participation) - Study Completion or Termination Visit |
| Change in Incremental Recovery (IR) at 30 Minutes Over Time | 0-30 minutes before infusion and 30 minutes post-infusion | The median changes in IR at 30 Minutes, calculated as the change in IR value from exposure day 1 (ED1). |
| Study Parts 1 and 3: Half Life (T 1/2) | 0-30 minutes before infusion up to 72 hours post-infusion | Elimination phase half-life will be determined as ln2/ λz. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Study Parts 1 and 3: Volume of Distribution at Steady State (Vss) | 0-30 minutes before infusion up to 72 hours post-infusion | Vss computed as CL·MRT. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) | ABR during prophylaxis (twice-weekly) in Part 2 was calculated as (Number of bleeding episodes/observed treatment period in days) \* 365.25. The treatment period on prophylaxis was defined as time between the first and the last prophylactic infusions and ABR on prophylaxis was calculated for participants who received a minimum of 3 months of prophylactic treatment with BAX326. |
| Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5) | The number of bleeding episodes treated with 1, 2, or ≥3 infusions of BAX326 to achieve adequate hemostasis. Only infusions required until resolution of bleed were considered. |
| Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3) | Rating Scale for Treatment of BEs (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. |
| Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) | — |
| Consumption of BAX326 Per Event Per Participant | Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) | Weight-adjusted consumption of BAX326 by event per participant, i.e., for prophylactic treatment and for treatment of bleeds until resolution of bleed. |
| Consumption of BAX326 Per Participant: Median Number of Infusions Per Month | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Occurrence of total binding antibodies of indeterminate specificity (within assay variability) to FIX, antibodies to CHO proteins and rFurin is defined by a dilution of 2 or less increase as compared to levels at screening visit (e.g. negative to 1:20 or 1:40). |
| Occurrence of Treatment Related Total Binding Antibodies | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Occurrence of treatment related total binding antibodies to Factor IX (FIX), antibodies to Chinese hamster ovary (CHO) proteins, and recombinant furin (rFurin) is defined by more than 2-dilution increase as compared to levels at screening visit and confirmed specificity (e.g. negative to 1:80) |
| Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis) | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Number of Participants Who Experienced Thrombotic Events | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Clinically significant changes in chemistry assessments for Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bicarbonate, Bilirubin, Blood Urea Nitrogen, Chloride, Glucose, Potassium, Protein (Serum), Sodium. Clinically Significant (CS) defined as: -1. The abnormal value constitutes an adverse event (AE) and, -2. The abnormal value is a symptom of or related to a disease that is already recorded as an AE in Case Report Form (CRF). |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Clinically significant changes in hematology assessments for Basophils, Basophils/Leukocytes, Eosinophils, Eosinophils/Leukocytes, Erythrocyte Mean Corpuscular Hemoglobin Concentration, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Lymphocytes/Leukocytes, Monocytes, Monocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes, Platelets, |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Clinically significant changes in vital signs assessments for pulse rate, systolic/diastolic blood pressure, respiratory rate, body temperature |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | Clinically significant changes in thrombogenic markers assessments for thrombin-antithrombin (TAT), prothrombin fragment 1.2, and D-dimer as evaluated by an independent Data Monitoring Committee (DMC) |
| Number of Adverse Events (AEs) After BAX326 Treatment | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. |
| EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better quality of life. |
| General Pain Assessment Through a Visual Analog Scale (VAS) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Participant rated assessment of health-related quality of life. The VAS Pain Scale rates current health state on a scale from 0 (no pain) to 100 (worst imaginable pain). For the pain scale, a higher score indicates worse pain. |
| Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. |
| SF-36: HRQoL 'Mental Health' (MH) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Physical Functioning' (PF) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Role-Physical (RP) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Role-Emotional | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Bodily Pain | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Mental Health | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Vitality | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL Social Functioning | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| SF-36: HRQoL General Health | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. |
| Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | 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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored. |
| Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | 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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored. |
| Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | 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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored. |
| Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | The Haem-A-QOL instrument has been developed and used in hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: physical health, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. For the Haem-A-QOL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100. |
| Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose) | 0-30 minutes before infusion up to 72 hours post-infusion | Defined as (AUC0-t + Ct)/ λz/ dose, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. |
| Health Resource Use - Number of Hospitalizations | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Health Resource Use - Total Days of Hospital Stay | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Health Resource Use - Emergency Room Visits | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Health Resource Use - Unscheduled Doctor's Office Visits | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Health Resource Use - Days Lost From Work or School | Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) | — |
| Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16) | Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) | 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. |
Countries
Argentina, Brazil, Bulgaria, Chile, Colombia, Czechia, Japan, Poland, Romania, Russia, Spain, Sweden, Ukraine, United Kingdom
Participant flow
Recruitment details
Enrollment was conducted at 29 clinical sites in South America, Europe, and Japan.
Pre-assignment details
86 enrolled. 1 withdrew consent prior to randomization. -31 were enrolled and randomized in Parts 1-3. Prior to receiving study drug: 3 discontinued by participant. -Part 2 an additional 54 were enrolled. Prior to receiving study drug: 3 discontinued by participant, 1 withdrew due to an AE, 2 screen failures, and 3 withdrew due to site closure.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Who Received Study Drug BAX326 : -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1 | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 2 -BAX326 Prophylaxis and On-demand | Physician Decision | 0 | 0 | 1 | 0 |
| Part 2 -BAX326 Prophylaxis and On-demand | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Part 3 -Pharmacokinetic BAX326 Only | Protocol Violation | 1 | 0 | 0 | 0 |
| Part 3 -Pharmacokinetic BAX326 Only | Required Emergency Surgery | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Participants Who Received Study Drug |
|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment Argentina | 2 Participants |
| Region of Enrollment Brazil | 1 Participants |
| Region of Enrollment Bulgaria | 10 Participants |
| Region of Enrollment Chile | 4 Participants |
| Region of Enrollment Colombia | 5 Participants |
| Region of Enrollment Czech Republic | 2 Participants |
| Region of Enrollment Japan | 5 Participants |
| Region of Enrollment Poland | 12 Participants |
| Region of Enrollment Romania | 8 Participants |
| Region of Enrollment Russian Federation | 12 Participants |
| Region of Enrollment Spain | 1 Participants |
| Region of Enrollment Sweden | 1 Participants |
| Region of Enrollment Ukraine | 8 Participants |
| Region of Enrollment United Kingdom | 2 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 73 |
| serious Total, serious adverse events | 4 / 73 |
Outcome results
Primary
Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose
Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2.
Time frame: 72 hours
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose | 14.30 (IU·hr/dL) / (IU/kg) |
| BeneFIX | Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose | 13.42 (IU·hr/dL) / (IU/kg) |
90% CI: [1.03, 1.09]
Secondary
Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause
The number of bleeding episodes treated with 1, 2, or ≥3 infusions of BAX326 to achieve adequate hemostasis. Only infusions required until resolution of bleed were considered.
Time frame: Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 26 Bleeding episodes |
| BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 16 Bleeding episodes |
| BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 65 Bleeding episodes |
| BeneFIX | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 21 Bleeding episodes |
| BeneFIX | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 57 Bleeding episodes |
| BeneFIX | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 12 Bleeding episodes |
| Study Part 3: BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 122 Bleeding episodes |
| Study Part 3: BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 28 Bleeding episodes |
| Study Part 3: BAX326 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 47 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 11 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 31 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 10 Bleeding episodes |
| Study Completion or Termination Visit | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 29 Bleeding episodes |
| Study Completion or Termination Visit | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 84 Bleeding episodes |
| Study Completion or Termination Visit | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 17 Bleeding episodes |
| Bleeding Cause: Injury | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 24 Bleeding episodes |
| Bleeding Cause: Injury | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 50 Bleeding episodes |
| Bleeding Cause: Injury | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 16 Bleeding episodes |
| Bleeding Cause: Unknown | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 1 infusion | 19 Bleeding episodes |
| Bleeding Cause: Unknown | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 3 or more infusions | 5 Bleeding episodes |
| Bleeding Cause: Unknown | Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause | 2 infusions | 5 Bleeding episodes |
Secondary
Change in Incremental Recovery (IR) at 30 Minutes Over Time
The median changes in IR at 30 Minutes, calculated as the change in IR value from exposure day 1 (ED1).
Time frame: 0-30 minutes before infusion and 30 minutes post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Change in Incremental Recovery (IR) at 30 Minutes Over Time | 0.03 (IU/dL) / (IU/kg) |
| BeneFIX | Change in Incremental Recovery (IR) at 30 Minutes Over Time | 0.075 (IU/dL) / (IU/kg) |
| Study Part 3: BAX326 | Change in Incremental Recovery (IR) at 30 Minutes Over Time | 0.06 (IU/dL) / (IU/kg) |
| Part 2 or Part 3: Week 26 | Change in Incremental Recovery (IR) at 30 Minutes Over Time | 0.12 (IU/dL) / (IU/kg) |
Secondary
Consumption of BAX326 Per Event Per Participant
Weight-adjusted consumption of BAX326 by event per participant, i.e., for prophylactic treatment and for treatment of bleeds until resolution of bleed.
Time frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Consumption of BAX326 Per Event Per Participant | 50.5 IU/kg |
| BeneFIX | Consumption of BAX326 Per Event Per Participant | 87.1 IU/kg |
Secondary
Consumption of BAX326 Per Participant: Median Number of Infusions Per Month
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Consumption of BAX326 Per Participant: Median Number of Infusions Per Month | 6.7 Infusions |
| BeneFIX | Consumption of BAX326 Per Participant: Median Number of Infusions Per Month | 2.7 Infusions |
Secondary
Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month | 347.8 IU/kg |
| BeneFIX | Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month | 167.3 IU/kg |
Secondary
EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores
EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.75 Score on a scale | Standard Deviation 0.16 |
| BeneFIX | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.75 Score on a scale | Standard Deviation 0.16 |
| Study Part 3: BAX326 | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.01 Score on a scale | Standard Deviation 0.18 |
| Part 2 or Part 3: Week 26 | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.72 Score on a scale | Standard Deviation 0.14 |
| Study Completion or Termination Visit | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.73 Score on a scale | Standard Deviation 0.09 |
| Bleeding Cause: Injury | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores | 0.00 Score on a scale | Standard Deviation 0.13 |
p-value: 0.779Paired t-test
p-value: 0.8999Paired t-test
Secondary
EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores
Participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better quality of life.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 58.75 Score on a scale | Standard Deviation 24.89 |
| BeneFIX | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 68.22 Score on a scale | Standard Deviation 22.78 |
| Study Part 3: BAX326 | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 9.98 Score on a scale | Standard Deviation 25.41 |
| Part 2 or Part 3: Week 26 | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 56.64 Score on a scale | Standard Deviation 25.97 |
| Study Completion or Termination Visit | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 62.07 Score on a scale | Standard Deviation 19 |
| Bleeding Cause: Injury | EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores | 5.43 Score on a scale | Standard Deviation 24.02 |
p-value: 0.0056Paired t-test
p-value: 0.413Paired t-test
Secondary
General Pain Assessment Through a Visual Analog Scale (VAS)
Participant rated assessment of health-related quality of life. The VAS Pain Scale rates current health state on a scale from 0 (no pain) to 100 (worst imaginable pain). For the pain scale, a higher score indicates worse pain.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | General Pain Assessment Through a Visual Analog Scale (VAS) | 32.67 Score on a scale | Standard Deviation 26.62 |
| BeneFIX | General Pain Assessment Through a Visual Analog Scale (VAS) | 33.09 Score on a scale | Standard Deviation 25.9 |
| Study Part 3: BAX326 | General Pain Assessment Through a Visual Analog Scale (VAS) | 0.35 Score on a scale | Standard Deviation 21.77 |
| Part 2 or Part 3: Week 26 | General Pain Assessment Through a Visual Analog Scale (VAS) | 47.57 Score on a scale | Standard Deviation 30.82 |
| Study Completion or Termination Visit | General Pain Assessment Through a Visual Analog Scale (VAS) | 39.93 Score on a scale | Standard Deviation 22.57 |
| Bleeding Cause: Injury | General Pain Assessment Through a Visual Analog Scale (VAS) | -7.64 Score on a scale | Standard Deviation 33.58 |
p-value: 0.9059Paired t-test
p-value: 0.4098Paired t-test
Secondary
Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL
The Haem-A-QOL instrument has been developed and used in hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: physical health, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. For the Haem-A-QOL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | 40.68 Score on a scale | Standard Deviation 15.33 |
| BeneFIX | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | 37.85 Score on a scale | Standard Deviation 16.57 |
| Study Part 3: BAX326 | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | -3.52 Score on a scale | Standard Deviation 12.81 |
| Part 2 or Part 3: Week 26 | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | 41.65 Score on a scale | Standard Deviation 15.19 |
| Study Completion or Termination Visit | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | 41.37 Score on a scale | Standard Deviation 16.64 |
| Bleeding Cause: Injury | Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL | -0.28 Score on a scale | Standard Deviation 12.18 |
p-value: 0.0633Paired t-test
p-value: 0.9363Paired t-test
Secondary
Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)
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 at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BAX326 | Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16) | 40.00 Score on a scale |
| BeneFIX | Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16) | 40.00 Score on a scale |
| Study Part 3: BAX326 | Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16) | 0.00 Score on a scale |
Secondary
Health Resource Use - Days Lost From Work or School
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 1 - Pharmacokinetics (N= 28, NA) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 2: Week 5 (N= 57, 14) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 2: Week 13 (N= 56, 12) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 2: Week 26 (N= 30, NA) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Part 3 (N= 25, NA) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Completion/Termination (N= 20, 9) | 0.0 Days |
| BAX326 | Health Resource Use - Days Lost From Work or School | Unscheduled Study Visit (N= 1, NA) | 0.0 Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Unscheduled Study Visit (N= 1, NA) | NA Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 1 - Pharmacokinetics (N= 28, NA) | NA Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 2: Week 26 (N= 30, NA) | NA Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Completion/Termination (N= 20, 9) | 0.0 Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 2: Week 5 (N= 57, 14) | 0.0 Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 3 (N= 25, NA) | NA Days |
| BeneFIX | Health Resource Use - Days Lost From Work or School | Part 2: Week 13 (N= 56, 12) | 0.0 Days |
Secondary
Health Resource Use - Emergency Room Visits
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Health Resource Use - Emergency Room Visits | Part 1 - Pharmacokinetics (N= 28, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Part 2: Week 5 (N= 57, 14) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Part 2: Week 13 (N= 56, 12) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Part 2: Week 26 (N= 30, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Part 3 (N= 25, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Completion/Termination (N= 20, 9) | 0.0 Visits |
| BAX326 | Health Resource Use - Emergency Room Visits | Unscheduled Study Visit (N= 1, NA) | 0.0 Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Unscheduled Study Visit (N= 1, NA) | NA Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 1 - Pharmacokinetics (N= 28, NA) | NA Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 2: Week 26 (N= 30, NA) | NA Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Completion/Termination (N= 20, 9) | 0.0 Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 2: Week 5 (N= 57, 14) | 0.0 Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 3 (N= 25, NA) | NA Visits |
| BeneFIX | Health Resource Use - Emergency Room Visits | Part 2: Week 13 (N= 56, 12) | 0.0 Visits |
Secondary
Health Resource Use - Number of Hospitalizations
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 1 - Pharmacokinetics (N= 28, NA) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 2: Week 5 (N= 57, 14) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 2: Week 13 (N= 56, 12) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 2: Week 26 (N= 30, NA) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Part 3 (N= 25, NA) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Completion/Termination (N= 20, 9) | 0.0 Hospitalizations |
| BAX326 | Health Resource Use - Number of Hospitalizations | Unscheduled Study Visit (N= 1, NA) | 0.0 Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Unscheduled Study Visit (N= 1, NA) | NA Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 1 - Pharmacokinetics (N= 28, NA) | NA Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 2: Week 26 (N= 30, NA) | NA Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Completion/Termination (N= 20, 9) | 0.0 Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 2: Week 5 (N= 57, 14) | 0.0 Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 3 (N= 25, NA) | NA Hospitalizations |
| BeneFIX | Health Resource Use - Number of Hospitalizations | Part 2: Week 13 (N= 56, 12) | 0.0 Hospitalizations |
Secondary
Health Resource Use - Total Days of Hospital Stay
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Health Resource Use - Total Days of Hospital Stay | Part 2: Week 5 (N= 1) | 46.0 Days |
| BAX326 | Health Resource Use - Total Days of Hospital Stay | Part 2: Week 13 (N= 1) | 23.0 Days |
| BAX326 | Health Resource Use - Total Days of Hospital Stay | Part 3 (N= 3) | 2.0 Days |
| BAX326 | Health Resource Use - Total Days of Hospital Stay | Completion/Termination (N= 2) | 5.5 Days |
Secondary
Health Resource Use - Unscheduled Doctor's Office Visits
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 1 - Pharmacokinetics (N= 28, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 5 (N= 57, 14) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 13 (N= 56, 12) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 26 (N= 30, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Part 3 (N= 25, NA) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Completion/Termination (N= 20, 9) | 0.0 Visits |
| BAX326 | Health Resource Use - Unscheduled Doctor's Office Visits | Unscheduled Study Visit (N= 1, NA) | 1.0 Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Unscheduled Study Visit (N= 1, NA) | NA Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 1 - Pharmacokinetics (N= 28, NA) | NA Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 26 (N= 30, NA) | NA Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Exposure Day 1 (N= 31, 14) | 0.0 Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Completion/Termination (N= 20, 9) | 0.0 Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 5 (N= 57, 14) | 0.0 Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 3 (N= 25, NA) | NA Visits |
| BeneFIX | Health Resource Use - Unscheduled Doctor's Office Visits | Part 2: Week 13 (N= 56, 12) | 0.0 Visits |
Secondary
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause
Rating Scale for Treatment of BEs (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: At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 5 Bleeding episodes |
| BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 53 Bleeding episodes |
| BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 3 Bleeding episodes |
| BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 46 Bleeding episodes |
| BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| BeneFIX | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 0 Bleeding episodes |
| BeneFIX | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 57 Bleeding episodes |
| BeneFIX | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| BeneFIX | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 32 Bleeding episodes |
| BeneFIX | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 1 Bleeding episodes |
| Study Part 3: BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 4 Bleeding episodes |
| Study Part 3: BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 103 Bleeding episodes |
| Study Part 3: BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 85 Bleeding episodes |
| Study Part 3: BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 5 Bleeding episodes |
| Study Part 3: BAX326 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 0 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 17 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 34 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| Part 2 or Part 3: Week 26 | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 1 Bleeding episodes |
| Study Completion or Termination Visit | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 51 Bleeding episodes |
| Study Completion or Termination Visit | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 2 Bleeding episodes |
| Study Completion or Termination Visit | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 2 Bleeding episodes |
| Study Completion or Termination Visit | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| Study Completion or Termination Visit | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 75 Bleeding episodes |
| Bleeding Cause: Injury | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 40 Bleeding episodes |
| Bleeding Cause: Injury | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 3 Bleeding episodes |
| Bleeding Cause: Injury | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| Bleeding Cause: Injury | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 45 Bleeding episodes |
| Bleeding Cause: Injury | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 2 Bleeding episodes |
| Bleeding Cause: Unknown | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | None | 0 Bleeding episodes |
| Bleeding Cause: Unknown | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Good | 17 Bleeding episodes |
| Bleeding Cause: Unknown | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Fair | 1 Bleeding episodes |
| Bleeding Cause: Unknown | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Excellent | 11 Bleeding episodes |
| Bleeding Cause: Unknown | Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause | Not Reported | 0 Bleeding episodes |
Secondary
Incremental Recovery (IR) at 30 Minutes Over Time
IR at 30 Minutes was measured at the following time points during the study: - Part 1 or Part 2, Exposure Day (ED) 1. (If participant was present for Study Part 1, then ED 1 from Part 1 was used. If Participant entered study in Study Part 2, then ED 1 from Part 2 was used.) - Part 2: Week 5 - Part 2: Week 13 - Part 2 or Part 3: Week 26 (Week 26 of study participation) - Study Completion or Termination Visit
Time frame: 0-30 minutes before infusion and 30 minutes post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Incremental Recovery (IR) at 30 Minutes Over Time | 0.78 (IU/dL) / (IU/kg) |
| BeneFIX | Incremental Recovery (IR) at 30 Minutes Over Time | 0.79 (IU/dL) / (IU/kg) |
| Study Part 3: BAX326 | Incremental Recovery (IR) at 30 Minutes Over Time | 0.83 (IU/dL) / (IU/kg) |
| Part 2 or Part 3: Week 26 | Incremental Recovery (IR) at 30 Minutes Over Time | 0.88 (IU/dL) / (IU/kg) |
| Study Completion or Termination Visit | Incremental Recovery (IR) at 30 Minutes Over Time | 0.89 (IU/dL) / (IU/kg) |
Secondary
Number of Adverse Events (AEs) After BAX326 Treatment
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Mild | 1 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Moderate | 1 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Severe | 3 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Unknown | 0 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Mild | 63 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Moderate | 17 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Severe | 1 adverse events |
| BAX326 | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Unknown | 1 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Unknown | 1 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Mild | 0 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Mild | 2 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Moderate | 0 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Severe | 0 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Severe | 0 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Moderate | 0 adverse events |
| BeneFIX | Number of Adverse Events (AEs) After BAX326 Treatment | Serious- Unknown | 0 adverse events |
Secondary
Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | 0 participants |
Secondary
Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis) | 0 participants |
Secondary
Number of Participants Who Experienced Thrombotic Events
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants Who Experienced Thrombotic Events | 0 participants |
Secondary
Number of Participants With Adverse Events (AEs) After BAX326 Treatment
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Mild | 1 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Mild | 33 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Severe | 2 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Moderate | 9 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Moderate | 1 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Severe | 1 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Unknown | 0 participants |
| BAX326 | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Unknown | 1 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Unknown | 0 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Mild | 0 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Moderate | 0 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Serious- Severe | 0 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Unknown | 1 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Mild | 1 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Moderate | 0 participants |
| BeneFIX | Number of Participants With Adverse Events (AEs) After BAX326 Treatment | Non-Serious- Severe | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry
Clinically significant changes in chemistry assessments for Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bicarbonate, Bilirubin, Blood Urea Nitrogen, Chloride, Glucose, Potassium, Protein (Serum), Sodium. Clinically Significant (CS) defined as: -1. The abnormal value constitutes an adverse event (AE) and, -2. The abnormal value is a symptom of or related to a disease that is already recorded as an AE in Case Report Form (CRF).
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology
Clinically significant changes in hematology assessments for Basophils, Basophils/Leukocytes, Eosinophils, Eosinophils/Leukocytes, Erythrocyte Mean Corpuscular Hemoglobin Concentration, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Lymphocytes/Leukocytes, Monocytes, Monocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes, Platelets,
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers
Clinically significant changes in thrombogenic markers assessments for thrombin-antithrombin (TAT), prothrombin fragment 1.2, and D-dimer as evaluated by an independent Data Monitoring Committee (DMC)
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs
Clinically significant changes in vital signs assessments for pulse rate, systolic/diastolic blood pressure, respiratory rate, body temperature
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAX326 | Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs | 0 participants |
Secondary
Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability)
Occurrence of total binding antibodies of indeterminate specificity (within assay variability) to FIX, antibodies to CHO proteins and rFurin is defined by a dilution of 2 or less increase as compared to levels at screening visit (e.g. negative to 1:20 or 1:40).
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) | Binding Antibody to Factor IX (FIX) | 6 participants |
| BAX326 | Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) | Antibody to Chinese hamster ovary (CHO) Protein | 0 participants |
| BAX326 | Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) | Antibody to recombinant Furin (rFurin) | 9 participants |
Secondary
Occurrence of Treatment Related Total Binding Antibodies
Occurrence of treatment related total binding antibodies to Factor IX (FIX), antibodies to Chinese hamster ovary (CHO) proteins, and recombinant furin (rFurin) is defined by more than 2-dilution increase as compared to levels at screening visit and confirmed specificity (e.g. negative to 1:80)
Time frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAX326 | Occurrence of Treatment Related Total Binding Antibodies | Binding Antibody to Factor IX (FIX) | 0 participants |
| BAX326 | Occurrence of Treatment Related Total Binding Antibodies | Antibody to Chinese hamster ovary (CHO) Protein | 0 participants |
| BAX326 | Occurrence of Treatment Related Total Binding Antibodies | Antibody to recombinant Furin (rFurin) | 0 participants |
Secondary
Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)
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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | 65.63 Score on a scale | Standard Deviation 13.26 |
| BeneFIX | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | 54.69 Score on a scale | Standard Deviation 6.63 |
| Study Part 3: BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | -10.94 Score on a scale | Standard Deviation 19.89 |
| Part 2 or Part 3: Week 26 | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | 65.63 Score on a scale | — |
| Study Completion or Termination Visit | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | 65.63 Score on a scale | — |
| Bleeding Cause: Injury | Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16) | 0.00 Score on a scale | — |
p-value: 0.5792Paired t-test
Secondary
Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)
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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | 63.33 Score on a scale | Standard Deviation 11.79 |
| BeneFIX | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | 55.83 Score on a scale | Standard Deviation 3.54 |
| Study Part 3: BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | -7.50 Score on a scale | Standard Deviation 8.25 |
| Part 2 or Part 3: Week 26 | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | 88.33 Score on a scale | — |
| Study Completion or Termination Visit | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | 86.67 Score on a scale | — |
| Bleeding Cause: Injury | Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16) | -1.67 Score on a scale | — |
p-value: 0.4208Paired t-test
Secondary
Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)
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. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: 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. 4 dimensions (physical, emotional, social, & school functioning) are scored.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | 64.13 Score on a scale | Standard Deviation 12.3 |
| BeneFIX | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | 55.43 Score on a scale | Standard Deviation 0 |
| Study Part 3: BAX326 | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | -8.70 Score on a scale | Standard Deviation 12.3 |
| Part 2 or Part 3: Week 26 | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | 80.43 Score on a scale | — |
| Study Completion or Termination Visit | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | 79.35 Score on a scale | — |
| Bleeding Cause: Injury | Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16) | -1.09 Score on a scale | — |
p-value: 0.5Paired t-test
Secondary
SF-36: HRQoL Bodily Pain
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Bodily Pain | 42.09 Score on a scale | Standard Deviation 10.21 |
| BeneFIX | SF-36: HRQoL Bodily Pain | 45.72 Score on a scale | Standard Deviation 8.68 |
| Study Part 3: BAX326 | SF-36: HRQoL Bodily Pain | 3.45 Score on a scale | Standard Deviation 9.95 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Bodily Pain | 36.89 Score on a scale | Standard Deviation 7.84 |
| Study Completion or Termination Visit | SF-36: HRQoL Bodily Pain | 39.33 Score on a scale | Standard Deviation 8.91 |
| Bleeding Cause: Injury | SF-36: HRQoL Bodily Pain | 2.44 Score on a scale | Standard Deviation 10.18 |
p-value: 0.0146Paired t-test
p-value: 0.4048Paired t-test
Secondary
SF-36: HRQoL General Health
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL General Health | 37.84 Score on a scale | Standard Deviation 8.38 |
| BeneFIX | SF-36: HRQoL General Health | 39.98 Score on a scale | Standard Deviation 9.03 |
| Study Part 3: BAX326 | SF-36: HRQoL General Health | 2.20 Score on a scale | Standard Deviation 8.22 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL General Health | 37.09 Score on a scale | Standard Deviation 10.47 |
| Study Completion or Termination Visit | SF-36: HRQoL General Health | 39.07 Score on a scale | Standard Deviation 8.88 |
| Bleeding Cause: Injury | SF-36: HRQoL General Health | 1.98 Score on a scale | Standard Deviation 7.94 |
p-value: 0.0562Paired t-test
p-value: 0.3864Paired t-test
Secondary
SF-36: HRQoL Mental Health
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Mental Health | 45.52 Score on a scale | Standard Deviation 8.78 |
| BeneFIX | SF-36: HRQoL Mental Health | 47.95 Score on a scale | Standard Deviation 8.84 |
| Study Part 3: BAX326 | SF-36: HRQoL Mental Health | 2.44 Score on a scale | Standard Deviation 11.29 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Mental Health | 45.46 Score on a scale | Standard Deviation 10.57 |
| Study Completion or Termination Visit | SF-36: HRQoL Mental Health | 42.64 Score on a scale | Standard Deviation 10.63 |
| Bleeding Cause: Injury | SF-36: HRQoL Mental Health | -2.82 Score on a scale | Standard Deviation 8.53 |
p-value: 0.1258Paired t-test
p-value: 0.2567Paired t-test
Secondary
SF-36: HRQoL 'Mental Health' (MH)
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL 'Mental Health' (MH) | 47.53 Score on a scale | Standard Deviation 9.46 |
| BeneFIX | SF-36: HRQoL 'Mental Health' (MH) | 49.67 Score on a scale | Standard Deviation 9.3 |
| Study Part 3: BAX326 | SF-36: HRQoL 'Mental Health' (MH) | 2.01 Score on a scale | Standard Deviation 11.17 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL 'Mental Health' (MH) | 47.24 Score on a scale | Standard Deviation 8.8 |
| Study Completion or Termination Visit | SF-36: HRQoL 'Mental Health' (MH) | 45.03 Score on a scale | Standard Deviation 9.96 |
| Bleeding Cause: Injury | SF-36: HRQoL 'Mental Health' (MH) | -2.21 Score on a scale | Standard Deviation 8.28 |
p-value: 0.2009Paired t-test
p-value: 0.3552Paired t-test
Secondary
SF-36: HRQoL Physical Functioning' (PF)
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Physical Functioning' (PF) | 40.20 Score on a scale | Standard Deviation 10.57 |
| BeneFIX | SF-36: HRQoL Physical Functioning' (PF) | 40.75 Score on a scale | Standard Deviation 10.14 |
| Study Part 3: BAX326 | SF-36: HRQoL Physical Functioning' (PF) | 0.68 Score on a scale | Standard Deviation 7.48 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Physical Functioning' (PF) | 40.04 Score on a scale | Standard Deviation 10.57 |
| Study Completion or Termination Visit | SF-36: HRQoL Physical Functioning' (PF) | 39.87 Score on a scale | Standard Deviation 10.55 |
| Bleeding Cause: Injury | SF-36: HRQoL Physical Functioning' (PF) | -0.16 Score on a scale | Standard Deviation 5.86 |
p-value: 0.5143Paired t-test
p-value: 0.9223Paired t-test
Secondary
SF-36: HRQoL Role-Emotional
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Role-Emotional | 44.22 Score on a scale | Standard Deviation 11.45 |
| BeneFIX | SF-36: HRQoL Role-Emotional | 44.80 Score on a scale | Standard Deviation 10.15 |
| Study Part 3: BAX326 | SF-36: HRQoL Role-Emotional | 0.37 Score on a scale | Standard Deviation 11.74 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Role-Emotional | 40.93 Score on a scale | Standard Deviation 9.1 |
| Study Completion or Termination Visit | SF-36: HRQoL Role-Emotional | 39.43 Score on a scale | Standard Deviation 11.57 |
| Bleeding Cause: Injury | SF-36: HRQoL Role-Emotional | -1.50 Score on a scale | Standard Deviation 8.91 |
p-value: 0.821Paired t-test
p-value: 0.5565Paired t-test
Secondary
SF-36: HRQoL Role-Physical (RP)
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Role-Physical (RP) | 40.39 Score on a scale | Standard Deviation 10.7 |
| BeneFIX | SF-36: HRQoL Role-Physical (RP) | 43.82 Score on a scale | Standard Deviation 8.67 |
| Study Part 3: BAX326 | SF-36: HRQoL Role-Physical (RP) | 3.47 Score on a scale | Standard Deviation 10.15 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Role-Physical (RP) | 39.15 Score on a scale | Standard Deviation 8.13 |
| Study Completion or Termination Visit | SF-36: HRQoL Role-Physical (RP) | 37.45 Score on a scale | Standard Deviation 10.12 |
| Bleeding Cause: Injury | SF-36: HRQoL Role-Physical (RP) | -1.70 Score on a scale | Standard Deviation 5.86 |
p-value: 0.0162Paired t-test
p-value: 0.3176Paired t-test
Secondary
SF-36: HRQoL Social Functioning
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Social Functioning | 41.80 Score on a scale | Standard Deviation 10.54 |
| BeneFIX | SF-36: HRQoL Social Functioning | 44.60 Score on a scale | Standard Deviation 8.94 |
| Study Part 3: BAX326 | SF-36: HRQoL Social Functioning | 2.78 Score on a scale | Standard Deviation 10.78 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Social Functioning | 43.42 Score on a scale | Standard Deviation 9.61 |
| Study Completion or Termination Visit | SF-36: HRQoL Social Functioning | 42.17 Score on a scale | Standard Deviation 9.8 |
| Bleeding Cause: Injury | SF-36: HRQoL Social Functioning | -1.26 Score on a scale | Standard Deviation 6.36 |
p-value: 0.0663Paired t-test
p-value: 0.489Paired t-test
Secondary
SF-36: HRQoL Vitality
Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | SF-36: HRQoL Vitality | 50.07 Score on a scale | Standard Deviation 8.47 |
| BeneFIX | SF-36: HRQoL Vitality | 52.75 Score on a scale | Standard Deviation 8.88 |
| Study Part 3: BAX326 | SF-36: HRQoL Vitality | 2.46 Score on a scale | Standard Deviation 10.75 |
| Part 2 or Part 3: Week 26 | SF-36: HRQoL Vitality | 50.17 Score on a scale | Standard Deviation 5.63 |
| Study Completion or Termination Visit | SF-36: HRQoL Vitality | 50.89 Score on a scale | Standard Deviation 6.81 |
| Bleeding Cause: Injury | SF-36: HRQoL Vitality | 0.72 Score on a scale | Standard Deviation 5.43 |
p-value: 0.1048Paired t-test
p-value: 0.641Paired t-test
Secondary
Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)
The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores.
Time frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BAX326 | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 39.08 Score on a scale | Standard Deviation 9.39 |
| BeneFIX | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 41.35 Score on a scale | Standard Deviation 8.73 |
| Study Part 3: BAX326 | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 2.60 Score on a scale | Standard Deviation 7.72 |
| Part 2 or Part 3: Week 26 | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 37.38 Score on a scale | Standard Deviation 7.2 |
| Study Completion or Termination Visit | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 38.92 Score on a scale | Standard Deviation 8.53 |
| Bleeding Cause: Injury | Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS) | 1.54 Score on a scale | Standard Deviation 5.11 |
p-value: 0.0189Paired t-test
p-value: 0.2974Paired t-test
Secondary
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326
ABR during prophylaxis (twice-weekly) in Part 2 was calculated as (Number of bleeding episodes/observed treatment period in days) \* 365.25. The treatment period on prophylaxis was defined as time between the first and the last prophylactic infusions and ABR on prophylaxis was calculated for participants who received a minimum of 3 months of prophylactic treatment with BAX326.
Time frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
Population: Full Analysis Set - Prophylactic cohort
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Joint bleeding episode | 0.00 Bleeds per year |
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Non-Joint bleeding episode | 0.00 Bleeds per year |
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Spontaneous bleeding episode | 0.00 Bleeds per year |
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Bleeding episode caused by injury | 0.00 Bleeds per year |
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | Unknown cause of bleeding episode | 0.00 Bleeds per year |
| BAX326 | Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 | All bleeding episodes | 1.99 Bleeds per year |
Secondary
Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)
Defined as (AUC0-t + Ct)/ λz/ dose, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 72 hours post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose) | 16.07 (IU·hr)/ dL/ (IU/kg) |
| BeneFIX | Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose) | 15.26 (IU·hr)/ dL/ (IU/kg) |
| Study Part 3: BAX326 | Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose) | 17.38 (IU·hr)/ dL/ (IU/kg) |
Secondary
Study Parts 1 and 3: Clearance (CL)
Computed as Dose/ AUC0-∞. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 72 hours post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Clearance (CL) | 0.0622 dL/(kg·hr) |
| BeneFIX | Study Parts 1 and 3: Clearance (CL) | 0.0655 dL/(kg·hr) |
| Study Part 3: BAX326 | Study Parts 1 and 3: Clearance (CL) | 0.0576 dL/(kg·hr) |
Secondary
Study Parts 1 and 3: Half Life (T 1/2)
Elimination phase half-life will be determined as ln2/ λz. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 72 hours post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Half Life (T 1/2) | 24.58 Hour |
| BeneFIX | Study Parts 1 and 3: Half Life (T 1/2) | 26.28 Hour |
| Study Part 3: BAX326 | Study Parts 1 and 3: Half Life (T 1/2) | 24.59 Hour |
Secondary
Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)
Defined as (Cmax - Cpre-infusion)/Dose, where maximum concentration (Cmax) will be determined as the highest concentration achieved within one hour after infusion. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 1 hour post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax) | 0.88 (IU/dL) / (IU/kg) |
| BeneFIX | Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax) | 0.73 (IU/dL) / (IU/kg) |
| Study Part 3: BAX326 | Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax) | 0.93 (IU/dL) / (IU/kg) |
Secondary
Study Parts 1 and 3: Mean Residence Time (MRT)
Computed as Area under the moment curve 0-∞ (AUMC0-∞) / AUC0-∞- TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration \[hr\] The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 72 hours post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Mean Residence Time (MRT) | 28.93 Hour |
| BeneFIX | Study Parts 1 and 3: Mean Residence Time (MRT) | 30.59 Hour |
| Study Part 3: BAX326 | Study Parts 1 and 3: Mean Residence Time (MRT) | 29.04 Hour |
Secondary
Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)
Vss computed as CL·MRT. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.
Time frame: 0-30 minutes before infusion up to 72 hours post-infusion
Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Study Parts 1 and 3: Volume of Distribution at Steady State (Vss) | 1.72 dL/kg |
| BeneFIX | Study Parts 1 and 3: Volume of Distribution at Steady State (Vss) | 1.98 dL/kg |
| Study Part 3: BAX326 | Study Parts 1 and 3: Volume of Distribution at Steady State (Vss) | 1.74 dL/kg |
Secondary
Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause
Time frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BAX326 | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 56.5 IU/kg |
| BeneFIX | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 59.0 IU/kg |
| Study Part 3: BAX326 | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 56.5 IU/kg |
| Part 2 or Part 3: Week 26 | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 68.7 IU/kg |
| Study Completion or Termination Visit | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 52.3 IU/kg |
| Bleeding Cause: Injury | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 70.0 IU/kg |
| Bleeding Cause: Unknown | Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause | 56.5 IU/kg |