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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-022726-33 | EudraCT Number |
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The purpose of this BAX 326 Continuation Study is to further investigate incremental recovery over time, the hemostatic efficacy, the safety, immunogenicity, and health-related quality of life (HR QoL) of BAX 326 in previously treated patients (PTPs) with severe and moderately severe hemophilia B who participated in BAX 326 pivotal study 250901 or BAX 326 pediatric study 251101.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BAX 326 | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BAX 326 (Recombinant factor IX) | Biological | The treatment with BAX 326 will be at the discretion of the investigator and will consist of either twice weekly prophylactic treatment with 50 IU/kg, modified prophylaxis, or on-demand treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events Possibly or Probably Related to the Investigational Product | Possibly or probably related adverse events that occurred during or after first BAX326 infusion. | Assessed (based on patient diary) every 3 months until study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode Required Until Bleed Resolution | Number of Infusions of BAX326 that were required until bleed resolution. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto de Hematología y Medicina Clíncia Rubén Dávoli | Rosario | 2000 | Argentina | |||
| UNIFESP - Universidade Estadual de Sao Paulo |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32866032 | Derived | Windyga J, Stasyshyn O, Lissitchkov T, Mamonov V, Serban M, Rusen L, Ploder B, Tangada S. Safety, Immunogenicity, and Hemostatic Efficacy of Nonacog Gamma in Patients With Severe or Moderately Severe Hemophilia B: A Continuation Study. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620950836. doi: 10.1177/1076029620950836. |
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Of 117 enrolled participants, 115 received treatment with IP. All 85 participants who transitioned from the pivotal/pediatric studies continued to receive IP in this study. Of the 32 newly recruited participants, 30 received treatment with IP. 1 participant did not meet the entry criteria and 1 participant discontinued the study prior treatment.
Enrollment was conducted at 40 clinical sites in 18 countries. A total of 117 participants were enrolled. Of these, 65 participants transitioned from BAX326 pivotal study, 20 participants transitioned from BAX326 pediatric study and 32 participants were newly recruited.
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| ID | Title | Description |
|---|---|---|
| FG000 | BAX 326 | Participants treated with BAX 326 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 19, 2015 | Jun 21, 2018 |
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| Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Overall clinical efficacy rating of bleeding episodes was done at resolution of bleed according these rating scale: Excellent=Full relief of pain and cessation of objective signs of bleeding after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusion would not affect the 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 a single infusion. Required more than 1 infusion for complete resolution. None=No improvement or condition worsens. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Annualized Bleed Rate During Prophylaxis Treatment | Annualized bleed rate (ABR) was calculated as (number of bleeding episodes/observed treatment period in days)*365.25 | For prophylactic treatment the period from first to last prophylactic infusion is considered. |
| Consumption of BAX 326: Number of Infusions Per Month and Per Year | The number of infusions consumed per month and per year for the prophylactic and on-demand treatment regimens. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Consumption of BAX 326: Weight Adjusted Consumption Per Month and Per Year | The weight adjusted consumption of BAX 326 per month and per year for the prophylactic and on-demand treatment regimens. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Consumption of BAX326: Weight Adjusted Consumption Per Bleeding Episode | The weight adjusted consumption of BAX 326 per bleeding episode for the prophylactic and on-demand treatment regimens. Only infusions required until the resolution of bleed are considered. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Development of Inhibitory and Total Binding Antibodies to Factor IX | Testing for inhibitory and total binding antibodies to Factor IX (FIX). Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening. | Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination. |
| Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin | Testing for antibodies to CHO proteins and rFurin. Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening. | Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination. |
| Occurrence of Severe Allergic Reactions and Thrombotic Events | The occurrence of severe allergic reactions and thrombotic events was assessed. | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
| Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs | Hematology panel consists of complete blood count (hemoglobin, hematocrit, erythrocytes, leukocytes) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet count. Clinical chemistry panel consists of sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine and glucose. Vital signs include body temperature, respiratory rate, pulse rate, supine systolic and diastolic blood pressure. CS=clinically significant, NCS=not clinically significant. Change from Screening to End of Study is reported. | Measurements at screening and at study completion/termination are included in the analysis. |
| Pharmacokinetics: Incremental Recovery (IR) Over Time | PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values. | IR over time was measured as Baseline and at Completion/Termination visit within 30 minutes pre-infusion and at 30 (± 5) minutes post-infusion. |
| Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞) | After a wash out period of at least 5 days PK infusion with investigational product was administered. AUC 0-∞ is defined as AUC 0-t + Ct/lambda z, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
| Pharmacokinetics: Elimination Phase Half-life (T1/2) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Elimination phase half-life is calculated as T1/2=log e (2) / lambda z where the elimination rate constant (lambda z) will be obtained by log e - linear fitting using least squares deviation to at least the last 3 quantifiable concentrations above pre-infusion level. | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
| Pharmacokinetics: Mean Residence Time (MRT) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Mean residence time is calculated as total area under the moment curve divided by the total area under the curve. MRT=(AUMC0-∞[h2*IU/dL])/(AUC0-∞[h*IU/dL]) - TI/2 where AUMC0-∞ is determined in a similar manner as AUC0-∞ and TI represents infusion duration in hours. | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
| Pharmacokinetics: Systemic Clearance (CL) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Systemic clearance is balculated as the dose in IU/kg divided by the total AUC. CL= Dose[IU/kg] / AUC0-∞[h*IU/dL] | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
| Pharmacokinetics: Volume of Distribution at Steady State (Vss) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Apparent steady state volume of distribution is calculated as Vss = CL * MRT CL=Systemic Clearance and MRT=Mean residence time | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
| Pharmacokinetics: Incremental Recovery (IR) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values. | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours. |
| Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 | The Short Form (36) Health Survey (SF-36) is a 36-item validated, generic HR QoL instrument suitable for participants of 17 years of age or older. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health, mental health, physical role functioning, emotional role functioning, social role functioning) which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. The mental health component summary score ranged from 19.5 to 64.2 with higher scores indicating less disability. The physical health component summary scores ranged from 18.6 to 59.6 with higher scores indicating less disability. | Baseline at exposure day 1 and at study completion/termination. |
| Changes in Health Related Quality of Life Using the Peds QL | The Pediatric Quality of Life Inventory (Peds QL) is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning and school functioning. The Peds-QL total score consist of all 23 items of all domains. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 44.6 to 98.9). The Peds-QL Physical Health Summary score consists of 8 items from the physical functioning domain. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 40.6 to 100.0) The Psychosocial Health Summary score consists of 15 items from the emotional, social and school functioning domains. Score range from 0 to 100 and higher scores indicate better quality of life (collected scores ranged from 46.7 to 100.0). | Baseline at exposure day 1 and at study completion/termination. |
| Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire Haemo-QoL and Haem-A-QoL | The Hemophilia Quality of Life Questionnaire (Haemo-QoL) and the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-Qol) instruments have 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. Haemo-QoL is used for participants aged 8 to 16 years and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 0.0 to 44.3) Haem-A-QoL is used for participants aged 17 years and older and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 4.9 to 76.8). | Baseline at exposure day 1 and at study completion/termination. |
| Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score. | The EQ-5D captures overall HR QoL (phyiscal, mental and social functioning). A health utility score can be calculated from this measure, adult and proxy versions available. EQ-5D Visual Analog Scale (EQ-5D VAS):Respondents specify their level of agreement to a statement by indicating a position along a continuous line between two endpoints (scale range from 0 to 100). Score 0 corresponds to the worst health you can imagine and score 100 corresponds to the best health you can imagine (collected scores ranged from 10-100). EQ-5D Total Index is based on general population valuation surveys. Responses to 5 questions are converted to an Index value and score range from 0 to 1, with higher scores indicating better quality of life. Total Index was derived on US population (collected scores ranged from 0.4-1). General pain assessment (Pain score) is done through a visual analog scale (VAS), scores ranging from 0 to 100 with higher scores indicating more pain (collected scores ranged 0-87). | Baseline at exposure day 1 and at study completion/termination. |
| São Paulo |
| 040024-002 |
| Brazil |
| Specialized Haematological Hospital "Joan Pavel" | Sofia | 1233 | Bulgaria |
| Hospital Dr. Sotero del Rio | Santiago | Chile |
| Hospital de San Jose | Bogotá | Colombia |
| Centro Medico Imbanaco | Cali | Colombia |
| Hospital Pablo Tobon Uribe | Medellín | 005543 | Colombia |
| Klinika detské hematologie a onkologie | Prague | 150 06 | Czechia |
| Maulana Azad Medical College and Associated Hospital | New Delhi | 110002 | India |
| St. James's Hospital, National Center for Hereditary Coagulation Disorders | Dublin | 8 | Ireland |
| University Hospital Policlinico Vittorio Emanuele, Hospital Ferrarotto Alessi | Catania | 95124 | Italy |
| University Hospital Careggi, Agency of Hemophilia - Regional Reference Center for Inherited Bleeding | Florence | 50134 | Italy |
| University of Foggia Riuniti Hospital, Department of Clinical and Experimental Medicine | Foggia | 71100 | Italy |
| Hospital San Giovanni Bosco, Center for Hemophilia and Thrombosis, Department of Hematology | Naples | 80144 | Italy |
| Padova University Hospital, Medical Clinic II, Center for Hemophilia | Padova | 35128 | Italy |
| Nara Medical University, Department of Pediatrics | Nara | 634-8251 | Japan |
| Tokyo Medical University | Tokyo | 160-0023 | Japan |
| Ogikubo Hospital | Tokyo | 167-0035 | Japan |
| Hematology and Transplantology Clinic, University Clinic Centre - Medical University Hospital | Gdansk | 80-952 | Poland |
| University Pediatric Hospital in Cracow | Krakow | 30-663 | Poland |
| Medical College of the Jagiellonian University, Department of Hematology | Krakow | 31-501 | Poland |
| Copernicus Hospital, Medical University in Lodz, Department of Hematology | Lodz | 93-510 | Poland |
| Professor Tadeusz Sokolowski Independent Public Teaching Hospital No. 1 of the Pomeranian Medical University in Szczecin | Szczecin | 71-252 | Poland |
| Klinika Hematologii | Warsaw | 00-579 | Poland |
| Institute of Haematology and Transfusion Medicine | Warsaw | 02-776 | Poland |
| Prof. Dr. C.T. Nicolau National Institute for Transfusional Hematology | Bucharest | 11156 | Romania |
| Louis Turcanu Emergency Clinical Children´s Hospital | Timișoara | Romania |
| Federal State Institution Kirov Hematology and Blood Transfusion Research Institute under the Federal Agency for High-Tech Medical Care | Kirov | 610027 | Russia |
| Pediatric Regional Clinical Hospital, Hematology Department | Krasnodar | 350007 | Russia |
| Hematology Research Center RAMS, Department of Reconstructive Orthopedics for Haemophilia Patients | Moscow | 125167 | Russia |
| Republican Center for Hemophilia Treatment Outpatient Clinic No. 37 | Saint Petersburg | 195213 | Russia |
| Regional clinical hospital | Yekaterinburg | 620149 | Russia |
| Malmö University Hospital, Department of Coagulation Disorders | Malmö | 205 02 | Sweden |
| Taipei Medical University Hospital | Taipei City | Taipei | 110 | Taiwan |
| Chung-Ho Memorial Hospital | Kaohsiung City | 807 | Taiwan |
| China Medical University Hospital | Taichung | 40447 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Taiwan University Hospital | Taipei | 10002 | Taiwan |
| Tri-Service General Hospital | Taipei | 114 | Taiwan |
| State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine" | Lviv | 79044 | Ukraine |
| Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Royal Free Hospital | London | NW3 2QG | United Kingdom |
| Manchester Children's Hospital | Manchester | M13 9WL | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | BAX 326 | Participants treated with BAX 326 |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | Adverse Events Possibly or Probably Related to the Investigational Product | Possibly or probably related adverse events that occurred during or after first BAX326 infusion. | Posted | Number | Adverse Events | Assessed (based on patient diary) every 3 months until study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
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| Secondary | Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode Required Until Bleed Resolution | Number of Infusions of BAX326 that were required until bleed resolution. | Only bleeding episodes that were exclusively treated with BAX 326 are considered. | Posted | Mean | Standard Deviation | Number of infusions | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). | Bleeding episodes | Bleeding episodes |
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| Secondary | Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed | Overall clinical efficacy rating of bleeding episodes was done at resolution of bleed according these rating scale: Excellent=Full relief of pain and cessation of objective signs of bleeding after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusion would not affect the 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 a single infusion. Required more than 1 infusion for complete resolution. None=No improvement or condition worsens. | Only bleeding episodes that were exclusively treated with BAX 326 are considered. | Posted | Number | Number of infusions | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). | Bleeding Episodes | Bleeding Episodes |
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| Secondary | Annualized Bleed Rate During Prophylaxis Treatment | Annualized bleed rate (ABR) was calculated as (number of bleeding episodes/observed treatment period in days)*365.25 | Only participants with an observation period of at least 3 months with BAX326 on prophylactic treatment were included in the analysis. | Posted | Median | Full Range | Bleeds per year | For prophylactic treatment the period from first to last prophylactic infusion is considered. |
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| Secondary | Consumption of BAX 326: Number of Infusions Per Month and Per Year | The number of infusions consumed per month and per year for the prophylactic and on-demand treatment regimens. | Posted | Mean | Standard Deviation | Number of infusions | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
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| Secondary | Consumption of BAX 326: Weight Adjusted Consumption Per Month and Per Year | The weight adjusted consumption of BAX 326 per month and per year for the prophylactic and on-demand treatment regimens. | Posted | Mean | Standard Deviation | IU/kg | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
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| Secondary | Consumption of BAX326: Weight Adjusted Consumption Per Bleeding Episode | The weight adjusted consumption of BAX 326 per bleeding episode for the prophylactic and on-demand treatment regimens. Only infusions required until the resolution of bleed are considered. | Posted | Mean | Standard Deviation | IU/kg | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). | Bleeding episodes | Bleeding episodes |
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| Secondary | Development of Inhibitory and Total Binding Antibodies to Factor IX | Testing for inhibitory and total binding antibodies to Factor IX (FIX). Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening. | Posted | Count of Participants | Participants | Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination. |
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| Secondary | Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin | Testing for antibodies to CHO proteins and rFurin. Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening. | Posted | Count of Participants | Participants | Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination. |
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| Secondary | Occurrence of Severe Allergic Reactions and Thrombotic Events | The occurrence of severe allergic reactions and thrombotic events was assessed. | Posted | Count of Participants | Participants | Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last). |
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| Secondary | Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs | Hematology panel consists of complete blood count (hemoglobin, hematocrit, erythrocytes, leukocytes) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet count. Clinical chemistry panel consists of sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine and glucose. Vital signs include body temperature, respiratory rate, pulse rate, supine systolic and diastolic blood pressure. CS=clinically significant, NCS=not clinically significant. Change from Screening to End of Study is reported. | Posted | Count of Participants | Participants | Measurements at screening and at study completion/termination are included in the analysis. |
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| Secondary | Pharmacokinetics: Incremental Recovery (IR) Over Time | PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values. | Analysis was done on all participants who received investigational product. All cases with a dosage higher than 120 IU/kg were excluded from the analysis. | Posted | Mean | Standard Deviation | (IU/dL):(IU/kg) | IR over time was measured as Baseline and at Completion/Termination visit within 30 minutes pre-infusion and at 30 (± 5) minutes post-infusion. |
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| Secondary | Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞) | After a wash out period of at least 5 days PK infusion with investigational product was administered. AUC 0-∞ is defined as AUC 0-t + Ct/lambda z, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | IU*hr/dL | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
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| Secondary | Pharmacokinetics: Elimination Phase Half-life (T1/2) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Elimination phase half-life is calculated as T1/2=log e (2) / lambda z where the elimination rate constant (lambda z) will be obtained by log e - linear fitting using least squares deviation to at least the last 3 quantifiable concentrations above pre-infusion level. | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | hours | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
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| Secondary | Pharmacokinetics: Mean Residence Time (MRT) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Mean residence time is calculated as total area under the moment curve divided by the total area under the curve. MRT=(AUMC0-∞[h2*IU/dL])/(AUC0-∞[h*IU/dL]) - TI/2 where AUMC0-∞ is determined in a similar manner as AUC0-∞ and TI represents infusion duration in hours. | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | hours | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
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| Secondary | Pharmacokinetics: Systemic Clearance (CL) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Systemic clearance is balculated as the dose in IU/kg divided by the total AUC. CL= Dose[IU/kg] / AUC0-∞[h*IU/dL] | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | dL/kg/hours | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
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| Secondary | Pharmacokinetics: Volume of Distribution at Steady State (Vss) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Apparent steady state volume of distribution is calculated as Vss = CL * MRT CL=Systemic Clearance and MRT=Mean residence time | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | dL/kg | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours |
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| Secondary | Pharmacokinetics: Incremental Recovery (IR) | PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values. | The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study. | Posted | Mean | Standard Deviation | (IU/dL):(IU/kg) | PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours. |
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| Secondary | Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 | The Short Form (36) Health Survey (SF-36) is a 36-item validated, generic HR QoL instrument suitable for participants of 17 years of age or older. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health, mental health, physical role functioning, emotional role functioning, social role functioning) which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. The mental health component summary score ranged from 19.5 to 64.2 with higher scores indicating less disability. The physical health component summary scores ranged from 18.6 to 59.6 with higher scores indicating less disability. | Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included. | Posted | Mean | Standard Deviation | Score on a scale | Baseline at exposure day 1 and at study completion/termination. |
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| Secondary | Changes in Health Related Quality of Life Using the Peds QL | The Pediatric Quality of Life Inventory (Peds QL) is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning and school functioning. The Peds-QL total score consist of all 23 items of all domains. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 44.6 to 98.9). The Peds-QL Physical Health Summary score consists of 8 items from the physical functioning domain. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 40.6 to 100.0) The Psychosocial Health Summary score consists of 15 items from the emotional, social and school functioning domains. Score range from 0 to 100 and higher scores indicate better quality of life (collected scores ranged from 46.7 to 100.0). | Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included. | Posted | Mean | Standard Deviation | Score on a scale | Baseline at exposure day 1 and at study completion/termination. |
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| Secondary | Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire Haemo-QoL and Haem-A-QoL | The Hemophilia Quality of Life Questionnaire (Haemo-QoL) and the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-Qol) instruments have 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. Haemo-QoL is used for participants aged 8 to 16 years and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 0.0 to 44.3) Haem-A-QoL is used for participants aged 17 years and older and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 4.9 to 76.8). | Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included. | Posted | Mean | Standard Deviation | Score on a scale | Baseline at exposure day 1 and at study completion/termination. |
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| Secondary | Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score. | The EQ-5D captures overall HR QoL (phyiscal, mental and social functioning). A health utility score can be calculated from this measure, adult and proxy versions available. EQ-5D Visual Analog Scale (EQ-5D VAS):Respondents specify their level of agreement to a statement by indicating a position along a continuous line between two endpoints (scale range from 0 to 100). Score 0 corresponds to the worst health you can imagine and score 100 corresponds to the best health you can imagine (collected scores ranged from 10-100). EQ-5D Total Index is based on general population valuation surveys. Responses to 5 questions are converted to an Index value and score range from 0 to 1, with higher scores indicating better quality of life. Total Index was derived on US population (collected scores ranged from 0.4-1). General pain assessment (Pain score) is done through a visual analog scale (VAS), scores ranging from 0 to 100 with higher scores indicating more pain (collected scores ranged 0-87). | Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included. | Posted | Mean | Standard Deviation | Score on a scale | Baseline at exposure day 1 and at study completion/termination. |
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Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BAX 326 | Participants treated with BAX 326 | 0 | 115 | 9 | 115 | 63 | 115 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
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| Duodenal ulcer hemorrhage | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
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| Corneal abscess | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Brain contusion | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Extradural hematoma | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Scroctal haematoma | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
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| Renal colic | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
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| Testicular appendage torsion | Reproductive system and breast disorders | MedDRA | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA | Non-systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA | Non-systematic Assessment |
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Agreements may vary with individual PIs, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or up to 2 years after study completion. The sponsor requires a review of results communication (e .g. for confidential information) ≥ 60 days prior to submission and may request an additional delay up to 6 months (e .g. for intellectual property protection). Prior authorization may be required.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 27, 2017 | Jun 21, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
Not provided
Not provided
| Asian |
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| Other |
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Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.
| OG004 | Overall Prophylaxis | All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis) |
| OG005 | On-Demand | All participants who received BAX 326 as on-demand regimen. |
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| Modified Prophylaxis |
Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated. |
| OG003 | PK Tailored Prophylaxis | Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg. |
| OG004 | Overall Prophylaxis | All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis) |
| OG005 | On-Demand | All participants who received BAX 326 as on-demand regimen. |
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All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)
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| OG004 | On-Demand | All participants who received BAX 326 as on-demand regimen. |
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| OG004 | On-Demand | All participants who received BAX 326 as on-demand regimen. |
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All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)
| OG004 | On-Demand | All participants who received BAX 326 as on-demand regimen. |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Severe allergic reactions |
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| Thrombotic events |
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