Back to resultsPivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BAX 326
BeneFIX
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B
Eligibility 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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
BAX 326
BeneFIX
Arm Description
Recombinant factor IX (rFIX)
Recombinant Factor IX (rFIX)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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
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).
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.
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.
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.
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.
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.
Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause
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.
Consumption of BAX326 Per Participant: Median Number of Infusions Per Month
Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month
Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
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).
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)
Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)
Number of Participants Who Experienced Thrombotic Events
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).
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,
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
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)
Number of Adverse Events (AEs) After BAX326 Treatment
Number of Participants With Adverse Events (AEs) After BAX326 Treatment
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Health Resource Use - Number of Hospitalizations
Health Resource Use - Total Days of Hospital Stay
Health Resource Use - Emergency Room Visits
Health Resource Use - Unscheduled Doctor's Office Visits
Health Resource Use - Days Lost From Work or School
Full Information
NCT ID
NCT01174446
First Posted
August 2, 2010
Last Updated
April 30, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT01174446
Brief Title
Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients
Official Title
Recombinant Factor IX (BAX 326): A Phase 1/3, Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety and Immunogenicity in Previously Treated Patients With Severe or Moderately Severe Hemophilia B
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
July 29, 2010 (Actual)
Primary Completion Date
May 3, 2012 (Actual)
Study Completion Date
May 3, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BAX 326
Arm Type
Experimental
Arm Description
Recombinant factor IX (rFIX)
Arm Title
BeneFIX
Arm Type
Active Comparator
Arm Description
Recombinant Factor IX (rFIX)
Intervention Type
Biological
Intervention Name(s)
BAX 326
Other Intervention Name(s)
Recombinant factor IX (rFIX), RIXUBIS
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
BeneFIX
Other Intervention Name(s)
Recombinant factor IX (rFIX)
Intervention Description
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
Primary Outcome Measure Information:
Title
Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose
Description
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
Secondary Outcome Measure Information:
Title
Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)
Description
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
Title
Study Parts 1 and 3: Mean Residence Time (MRT)
Description
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
Title
Study Parts 1 and 3: Clearance (CL)
Description
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
Title
Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)
Description
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
Title
Incremental Recovery (IR) at 30 Minutes Over Time
Description
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
Title
Change in Incremental Recovery (IR) at 30 Minutes Over Time
Description
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
Title
Study Parts 1 and 3: Half Life (T 1/2)
Description
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
Title
Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)
Description
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
Title
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326
Description
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)
Title
Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause
Description
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)
Title
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause
Description
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)
Title
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)
Title
Consumption of BAX326 Per Event Per Participant
Description
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)
Title
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)
Title
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)
Title
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)
Title
Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability)
Description
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)
Title
Occurrence of Treatment Related Total Binding Antibodies
Description
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)
Title
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)
Title
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)
Title
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry
Description
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)
Title
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology
Description
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)
Title
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs
Description
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)
Title
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers
Description
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)
Title
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)
Title
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)
Title
EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores
Description
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)
Title
EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores
Description
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)
Title
General Pain Assessment Through a Visual Analog Scale (VAS)
Description
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)
Title
Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)
Description
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)
Title
SF-36: HRQoL 'Mental Health' (MH)
Description
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)
Title
SF-36: HRQoL Physical Functioning' (PF)
Description
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)
Title
SF-36: HRQoL Role-Physical (RP)
Description
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)
Title
SF-36: HRQoL Role-Emotional
Description
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)
Title
SF-36: HRQoL Bodily Pain
Description
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)
Title
SF-36: HRQoL Mental Health
Description
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)
Title
SF-36: HRQoL Vitality
Description
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)
Title
SF-36: HRQoL Social Functioning
Description
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)
Title
SF-36: HRQoL General Health
Description
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)
Title
Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)
Description
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)
Title
Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)
Description
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)
Title
Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)
Description
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)
Title
Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL
Description
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)
Title
Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)
Description
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Rosario
Country
Argentina
City
Brasilia
Country
Brazil
City
Sao Paulo
Country
Brazil
City
Sofia
Country
Bulgaria
City
Santiago
Country
Chile
City
Bogotá
Country
Colombia
City
Cali
Country
Colombia
City
Prague
Country
Czechia
City
Hiroshima
Country
Japan
City
Nara
Country
Japan
City
Tochigi
Country
Japan
City
Tokyo
Country
Japan
City
Gdansk
Country
Poland
City
Krakow
Country
Poland
City
Lodz
Country
Poland
City
Warsaw
Country
Poland
City
Bucharest
Country
Romania
City
Timisoara
Country
Romania
City
Kirov
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
Barcelona
Country
Spain
City
Malmö
Country
Sweden
City
Lviv
Country
Ukraine
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23834666
Citation
Windyga J, Lissitchkov T, Stasyshyn O, Mamonov V, Rusen L, Lamas JL, Oh MS, Chapman M, Fritsch S, Pavlova BG, Wong WY, Abbuehl BE. Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level </=2%) haemophilia B. Haemophilia. 2014 Jan;20(1):15-24. doi: 10.1111/hae.12228. Epub 2013 Jul 9.
Results Reference
result
Learn more about this trial
Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients
We'll reach out to this number within 24 hrs