Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01174446
• Other study ID #: 250901
• Secondary ID: 2009-016720-31
• Status: Completed
• Phase: Phase 3
• Start date: July 29, 2010
• Est. completion date: May 3, 2012

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: May 3, 2012
• Est. primary completion date: May 3, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• BAX 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
• BeneFIX
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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Countries where clinical trial is conducted

Argentina,  Brazil,  Bulgaria,  Chile,  Colombia,  Czechia,  Japan,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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 ?z. ?z was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2.	72 hours
Secondary	Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-8/ Dose)	Defined as (AUC0-t + Ct)/ ?z/ dose, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. ?z 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.	0-30 minutes before infusion up to 72 hours post-infusion
Secondary	Study Parts 1 and 3: Mean Residence Time (MRT)	Computed as Area under the moment curve 0-8 (AUMC0-8) / AUC0-8- TI/2, where AUMC0-8 will be determined in a similar manner as AUC0-8 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.	0-30 minutes before infusion up to 72 hours post-infusion
Secondary	Study Parts 1 and 3: Clearance (CL)	Computed as Dose/ AUC0-8. 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.	0-30 minutes before infusion up to 72 hours post-infusion
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.	0-30 minutes before infusion up to 1 hour post-infusion
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	0-30 minutes before infusion and 30 minutes post-infusion
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).	0-30 minutes before infusion and 30 minutes post-infusion
Secondary	Study Parts 1 and 3: Half Life (T 1/2)	Elimination phase half-life will be determined as ln2/ ?z. 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.	0-30 minutes before infusion up to 72 hours post-infusion
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.	0-30 minutes before infusion up to 72 hours post-infusion
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.	Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
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.	Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5)
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.	At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3)
Secondary	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)
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.	Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
Secondary	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)
Secondary	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)
Secondary	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)
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).	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
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)	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Secondary	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)
Secondary	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)
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).	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
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,	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
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	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
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)	Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Secondary	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)
Secondary	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)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
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.	Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)