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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000413-39 | EudraCT Number |
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The purpose of the study is to assess the hemostatic efficacy and safety of BAX 326 in subjects with severe (FIX level < 1%) or moderately severe (FIX level 1-2%) hemophilia B undergoing major or minor elective or emergency surgical, dental or other invasive procedures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BAX326 in Surgery | Experimental | BAX 326 (recombinant factor IX) in Surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant factor IX | Biological | Following a loading dose with BAX326, participants will receive BAX326 as a bolus infusion. The treatment regimen will be determined by the intensity and duration of the hemostatic challenge and the institution´s standard of care. The dose will be tailored to raise FIX concentration to at least 80%-100% of normal for major surgeries and to at least 30%-60% of normal for minor surgeries. |
| Measure | Description | Time Frame |
|---|---|---|
| Intraoperative Hemostatic Efficacy | Assessment by the operating surgeon on a 4 point ordinal scale (according to the definitions provided below): - Excellent: Intraoperative blood loss was less than or equal to that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% ) - Good: Intraoperative blood loss was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101 - 150%) - Fair: Intraoperative blood loss was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%) - None: Uncontrolled hemorrhage that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | On day of surgery |
| Actual Intraoperative Blood Loss | Actual intraoperative blood loss was determined by the drainage volume, if a drain was placed, and the estimated blood loss into swabs and towels during the procedure. | On day of surgery |
| Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon | Predicted average/maximum blood loss minus actual blood loss. Prior to the surgery, the surgeon predicted the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study participant for the intraoperative period. | On day of surgery |
| Postoperative Hemostatic Efficacy at Drain Removal | The postoperative hemostatic efficacy was to be assessed by the operating surgeon according to the following criteria (4-point ordinal scale): - Excellent: Volume in drain was less than or equal than that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% ) - Good: Volume in drain was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101% - 150%) - Fair: Volume in drain was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%) - None: Uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate |
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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 Clínica Rubén Dávoli | Rosario | 2000 | Argentina | |||
| Specialized Haematological Hospital "Joan Pavel" |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24697870 | Result | Windyga J, Lissitchkov T, Stasyshyn O, Mamonov V, Ghandehari H, Chapman M, Fritsch S, Wong WY, Pavlova BG, Abbuehl BE. Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study. Haemophilia. 2014 Sep;20(5):651-8. doi: 10.1111/hae.12419. Epub 2014 Apr 3. | |
| 32816519 |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
30 unique participants enrolled for 41 surgical procedures, of which 1 participant discontinued before treatment with BAX326 but re-enrolled later for another surgical procedure. Note: a unique participant can undergo more than one surgical procedure.
Enrollment was conducted at 10 clinical sites in 8 countries (Bulgaria, Czech Republic, Poland, Romania, Russia, Ukraine, Chile, Colombia).
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment With BAX326 | Recombinant Factor IX (FIX): Following a loading dose with BAX326, participants received BAX326 as a bolus infusion. The treatment regimen was determined by the intensity and duration of the hemostatic challenge and the institution's standard of care. The dose was tailored to raise FIX concentration to at least 80%-100% of normal for major surgeries and to at least 30%-60% of normal for minor surgeries. Note: Treatment with BAX326 refers to unique participants treated with BAX326 which is less than the number of participants treated with BAX326 as unique participants could undergo more than one surgical procedure in this study. 30 unique participants were treated with BAX326 for 40 planned surgical procedures; of these, 2 unique participants were treated with BAX326 but did not undergo 2 surgical procedures (1 surgery per unique participant), therefore 28 unique participants underwent 38 surgical procedures. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Note there were 30 unique participants with a total of 40 planned surgeries, as participants may have > 1 surgery. Baseline data reflects number of planned surgeries.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment With BAX326 | Recombinant Factor IX (FIX): Following a loading dose with BAX326, participants received BAX326 as a bolus infusion. The treatment regimen was determined by the intensity and duration of the hemostatic challenge and the institution's standard of care. The dose was tailored to raise FIX concentration to at least 80%-100% of normal for major surgeries and to at least 30%-60% of normal for minor surgeries. Note: Treatment with BAX326 refers to unique participants treated with BAX326 which is less than the number of participants treated with BAX326 as unique participants could undergo more than one surgical procedure in this study. 30 unique participants were treated with BAX326 for 40 planned surgical procedures; of these, 2 unique participants were treated with BAX326 but did not undergo 2 surgical procedures (1 surgery per unique participant), therefore 28 unique participants underwent 38 surgical procedures. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Intraoperative Hemostatic Efficacy | Assessment by the operating surgeon on a 4 point ordinal scale (according to the definitions provided below): - Excellent: Intraoperative blood loss was less than or equal to that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% ) - Good: Intraoperative blood loss was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101 - 150%) - Fair: Intraoperative blood loss was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%) - None: Uncontrolled hemorrhage that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 and had surgery. Note: a unique participant could have more than one surgical procedure. | Posted | Number | surgeries | On day of surgery | surgeries | surgeries |
|
Throughout the study period (approximately 2 years 5 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All unique participants treated with BAX326 per planned surgical procedure. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post procedural swelling | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
Data provided for surgical procedures, treatments with BAX326 etc. and for unique participants (one unique participant could undergo more than one surgical procedure).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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|
|
| At drain removal (from 1-3 days postoperatively) |
| Postoperative Hemostatic Efficacy at Postoperative Day 3 | Assessment by the operating surgeon on a 4 point ordinal scale: - Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant - Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant - Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate - None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | At postoperative day 3 (approximately 72 hours postoperatively) |
| Postoperative Hemostatic Efficacy on Day of Discharge | Assessment by the operating surgeon on a 4 point ordinal scale: - Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant - Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant - Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate - None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | At discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) |
| Actual Postoperative Blood Loss | Postoperative blood loss was based on the drainage fluid and was only assessed for participants who had a drain placed during surgery. | At drain removal (from 1-3 days postoperatively) |
| Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon | Predicted average/maximum blood loss minus actual blood loss for participants who had a drain placed during surgery. Prior to the surgery, the surgeon will predict the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study subject for the postoperative period until drain removal. | At postoperative day 3 (approximately 72 hours postoperatively) |
| Daily Weight-Adjusted Dose of BAX326 Per Participant | Daily weight-adjusted doses of BAX326 per participant were recorded from the day of surgery until postoperative Days 11+. Each category in outcome measure includes number of all, major and minor surgeries, respectively, if different from the totals. | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) |
| Total Weight-Adjusted Dose of BAX326 Per Participant | Assessed for the intra- and postoperative periods. | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) |
| Number of Units of Blood Product Transfused | Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both. | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) |
| Volume of Blood Product Transfused | Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both. | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) |
| Safety: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | Throughout the study period (approximately 2 years 5 months) |
| Safety: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | If there was more than 2-dilution increase as compared to pre-study level at screening. | Throughout the study period (approximately 2 years 5 months) |
| Safety: Number of Adverse Events Related to BAX326 | Throughout the study period (approximately 2 years 5 months) |
| Safety: Occurence of a Thrombotic Event | Throughout the study period (approximately 2 years 5 months) |
| Pre-Surgical Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 72 Hours Post-infusion Per Dose | AUC0-72h (area under the plasma concentration/time curve from time 0 to 72 hours) was 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 R2. | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Pre-Surgical Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve Per Dose (Total AUC/Dose) | Total AUC/Dose is also AUC0-inf (area under the plasma concentration/time curve from time 0 to infinity) and was defined as AUC0-t + Ct / λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration and λz is the terminal rate constant. | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Pre-Surgical Pharmacokinetics (PK): Mean Residence Time (MRT) | The MRT is the average time that the study product stays in the body (or plasma) and is calculated as: AUMC 0-inf / AUC 0-inf, where AUMC 0-inf was determined in a similar manner as AUC 0-inf. | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Pre-Surgical Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | CL is the volume of plasma which is completely cleared of study product per unit time and is calculated as the dose divided by the total area under the curve from 0 to infinity (AUC0-inf). | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Pre-Surgical Pharmacokinetics (PK): Incremental Recovery (IR) at 30 Min | IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 30±5 minutes for pre-surgical PK. | Within 30 mins pre-infusion and post-infusion at 30 minutes |
| Pre-Surgical Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | T1/2 was determined as ln2 / λz. | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Pre-Surgical Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | Vss was computed as CL·MRT. | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr |
| Incremental Recovery (IR) at 15±5 Minutes Following Loading Dose Prior to Surgery | IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 15±5 minutes for the loading dose. | Within 60 minutes prior to surgery and 15 ± 5 minutes after loading dose/rebolus, if applicable. |
| Sofia |
| 1233 |
| Bulgaria |
| Hospital Dr. Sotero del Rio | Santiago | Chile |
| Centro Medico Imbanaco | Cali | Colombia |
| Klinika detska hematologie a onkologie, Fakultni Nemocnice Motol | Prague | 150 06 | Czechia |
| Medical University Lodz, Copernicus Hospital, Department of Hematology | Lodz | 93-510 | Poland |
| Independent Public Pediatric Teaching Hospital, Clinical Department of Hematology and Pediatrics | Warsaw | 00-579 | Poland |
| Institute of Haematology and Transfusion Medicine | Warsaw | 02-776 | Poland |
| 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 |
| Children's Territorial Clinical Hospital | Krasnodar | 350007 | Russia |
| Hematology Research Center RAMS | Moscow | 125167 | Russia |
| State Institution "Institute of Blood Pathology and Transfusion Medicine under the Academy of Medical Sciences of Ukraine" | Lviv | 79044 | Ukraine |
| Royal Manchester Children's Hospital, Department of Hematology | Manchester | M13 9WL | United Kingdom |
| Derived |
| Windyga J, Timofeeva M, Stasyshyn O, Mamonov V, Lamas Castellanos JL, Lissitchkov T, Chojnowski K, Chapman M, Pavlova BG, Tangada S. Phase 3 Clinical Trial: Perioperative Use of Nonacog Gamma, a Recombinant Factor IX, in Previously Treated Patients With Moderate/Severe Hemophilia B. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620946839. doi: 10.1177/1076029620946839. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | All Surgeries | All participants treated with BAX326 per surgical procedure. Data is reported per number of surgical procedures as opposed to number of unique participants as a unique participant can have more than one surgical procedure. |
| OG001 | Major Surgeries | Major surgery defined as surgeries which required moderate or deep sedation, general anesthesia, or major conduction blockade for patient comfort. It generally referred to major orthopedic (e.g., joint replacement), major abdominal, intracranial, cardiovascular, spinal and any other surgery which had a significant risk of large volume blood loss or blood loss into a confined anatomical space. Several tooth extractions or extraction of the third molar were generally considered as major. |
| OG002 | Minor Surgeries | Minor surgery defined as surgeries which could be safely and comfortably performed on a patient who had received local or topical anesthesia, without more than minimal pre-operative medication or minimal pre-operative medication or minimal intraoperative sedation. The likelihood of complications requiring hospitalization or prolonged hospitalization was remote. It referred to interventions such as removal of skin lesions, arthroscopy, minor dental procedures or dental extractions. |
|
|
| Primary | Actual Intraoperative Blood Loss | Actual intraoperative blood loss was determined by the drainage volume, if a drain was placed, and the estimated blood loss into swabs and towels during the procedure. | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 per surgical procedure. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | mL | On day of surgery | surgeries | surgeries |
|
|
|
| Primary | Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon | Predicted average/maximum blood loss minus actual blood loss. Prior to the surgery, the surgeon predicted the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study participant for the intraoperative period. | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 per surgical procedure. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | mL | On day of surgery | surgeries | surgeries |
|
|
|
| Primary | Postoperative Hemostatic Efficacy at Drain Removal | The postoperative hemostatic efficacy was to be assessed by the operating surgeon according to the following criteria (4-point ordinal scale): - Excellent: Volume in drain was less than or equal than that expected for the type of procedure performed in a hemostatically normal participant (≤ 100% ) - Good: Volume in drain was up to 50% more than expected for the type of procedure performed in a hemostatically normal participant (101% - 150%) - Fair: Volume in drain was more than 50% of that expected for the type of procedure performed in a hemostatically normal participant (> 150%) - None: Uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | Participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who had a drain placed during surgery (major surgeries only). Note: a unique participant could have more than one surgical procedure | Posted | Number | major surgeries with drain placed | At drain removal (from 1-3 days postoperatively) | major surgeries with drain placed | major surgeries with drain placed |
|
|
|
| Primary | Postoperative Hemostatic Efficacy at Postoperative Day 3 | Assessment by the operating surgeon on a 4 point ordinal scale: - Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant - Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant - Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate - None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | Participants in the Full Analysis Set who were provided with a hemostatic efficacy assessment by the operating surgeon at post operative day 3 where no drain was employed. Note: a unique participant could have more than one surgical procedure. | Posted | Number | surgeries | At postoperative day 3 (approximately 72 hours postoperatively) | surgeries | surgeries |
|
|
|
| Primary | Postoperative Hemostatic Efficacy on Day of Discharge | Assessment by the operating surgeon on a 4 point ordinal scale: - Excellent: Postoperative hemostasis achieved with BAX326 was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal participant - Good: Postoperative hemostasis achieved with BAX326 was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal participant - Fair: Postoperative hemostasis with BAX326 was clearly less than optimal for the type of procedure performed but was maintained without the need to change the Factor IX concentrate - None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of Factor IX concentrate | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 per surgical procedure. Note: a unique participant could have more than one surgical procedure. | Posted | Number | surgeries | At discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) | surgeries | surgeries |
|
|
|
| Primary | Actual Postoperative Blood Loss | Postoperative blood loss was based on the drainage fluid and was only assessed for participants who had a drain placed during surgery. | Participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who had a drain placed during surgery (major surgeries only). Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | mL | At drain removal (from 1-3 days postoperatively) | surgeries with drain placed | surgeries with drain placed |
|
|
|
| Primary | Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon | Predicted average/maximum blood loss minus actual blood loss for participants who had a drain placed during surgery. Prior to the surgery, the surgeon will predict the estimated volume (mL) of the expected average and maximum blood loss for the planned surgical intervention in a hemostatically normal individual of the same sex, age, and stature as the study subject for the postoperative period until drain removal. | Participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who had a drain placed during surgery (major surgeries only). Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | mL | At postoperative day 3 (approximately 72 hours postoperatively) | surgeries with drain placed | surgeries with drain placed |
|
|
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| Primary | Daily Weight-Adjusted Dose of BAX326 Per Participant | Daily weight-adjusted doses of BAX326 per participant were recorded from the day of surgery until postoperative Days 11+. Each category in outcome measure includes number of all, major and minor surgeries, respectively, if different from the totals. | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 per surgical procedure. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | IU/kg | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) | surgeries | surgeries |
|
|
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| Primary | Total Weight-Adjusted Dose of BAX326 Per Participant | Assessed for the intra- and postoperative periods. | All participants in the Full Analysis Set (participants exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) treated with BAX326 per surgical procedure. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | IU/kg | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) | surgeries | surgeries |
|
|
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| Primary | Number of Units of Blood Product Transfused | Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both. | Participants in the Full Analysis Set (exposed to BAX326 and provided suitable hemostatic efficacy data) who received blood product infusions during the intraoperative and/or postoperative period. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | units | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) | surgery where blood transfusion given | surgery where blood transfusion given |
|
|
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| Primary | Volume of Blood Product Transfused | Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both. | Participants in the Full Analysis Set (exposed to BAX326 and provided suitable hemostatic efficacy data) who received blood product infusions during the intraoperative and/or postoperative period. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | mL | From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery) | surgery where blood transfusion given | surgery where blood transfusion given |
|
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| Primary | Safety: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX) | All participants in the Safety Analysis Set (participants exposed to BAX326 during the study). Note: a unique participant could be treated with BAX326 for more than one surgical procedure. | Posted | Number | participants | Throughout the study period (approximately 2 years 5 months) | treatments with BAX326 before surgery | treatments with BAX326 before surgery |
|
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| Primary | Safety: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX) | If there was more than 2-dilution increase as compared to pre-study level at screening. | All participants in the Safety Analysis Set (participants exposed to BAX326 during the study). Note: a unique participant could be treated with BAX326 for more than one surgical procedure. | Posted | Number | participants | Throughout the study period (approximately 2 years 5 months) | treatments with BAX326 before surgery | treatments with BAX326 before surgery |
|
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| Primary | Safety: Number of Adverse Events Related to BAX326 | All participants in the Safety Analysis Set (participants exposed to BAX326 during the study). Note: a unique participant could be treated with BAX326 for more than one surgical procedure. | Posted | Number | adverse events | Throughout the study period (approximately 2 years 5 months) | treatments with BAX326 before surgery | treatments with BAX326 before surgery |
|
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| Primary | Safety: Occurence of a Thrombotic Event | All participants in the Safety Analysis Set (participants exposed to BAX326 during the study). Note: a unique participant could be treated with BAX326 for more than one surgical procedure. | Posted | Number | surgeries | Throughout the study period (approximately 2 years 5 months) | treatments with BAX326 before surgery | treatments with BAX326 before surgery |
|
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| Primary | Pre-Surgical Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 72 Hours Post-infusion Per Dose | AUC0-72h (area under the plasma concentration/time curve from time 0 to 72 hours) was 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 R2. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | [IU•hour (hr)/dL] : IU/kg | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
|
|
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| Primary | Pre-Surgical Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve Per Dose (Total AUC/Dose) | Total AUC/Dose is also AUC0-inf (area under the plasma concentration/time curve from time 0 to infinity) and was defined as AUC0-t + Ct / λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration and λz is the terminal rate constant. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | [IU•hour (hr)/dL] : IU/kg | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
|
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| Primary | Pre-Surgical Pharmacokinetics (PK): Mean Residence Time (MRT) | The MRT is the average time that the study product stays in the body (or plasma) and is calculated as: AUMC 0-inf / AUC 0-inf, where AUMC 0-inf was determined in a similar manner as AUC 0-inf. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | hours (hr) | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
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| Primary | Pre-Surgical Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL) | CL is the volume of plasma which is completely cleared of study product per unit time and is calculated as the dose divided by the total area under the curve from 0 to infinity (AUC0-inf). | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | dL/(kg•hr) | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
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| Primary | Pre-Surgical Pharmacokinetics (PK): Incremental Recovery (IR) at 30 Min | IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 30±5 minutes for pre-surgical PK. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | IU/dL : IU/kg | Within 30 mins pre-infusion and post-infusion at 30 minutes | pre-surgical PK assessments | pre-surgical PK assessments |
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| Primary | Pre-Surgical Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2) | T1/2 was determined as ln2 / λz. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | hours (hr) | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
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| Primary | Pre-Surgical Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss) | Vss was computed as CL·MRT. | Participants in the Full Analysis Set (exposed to BAX326 and provided data suitable for hemostatic efficacy analysis) who underwent a pre-surgical PK assessment in this study i.e.not participants who underwent a PK assessment in the pivotal study (250901). Note: a unique participant could have a pre-surgical PK assessment for more than one surgery. | Posted | Mean | Standard Deviation | dL/kg | Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr | pre-surgical PK assessments | pre-surgical PK assessments |
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| Primary | Incremental Recovery (IR) at 15±5 Minutes Following Loading Dose Prior to Surgery | IR was defined as (C post-infusion - C pre-infusion) / Dose, where C post-infusion is the measured concentration achieved at 15±5 minutes for the loading dose. | Participants in the Full Analysis Set (exposed to BAX326 and provided suitable hemostatic efficacy data) who provided data for incremental recovery (IR) after the loading dose prior to surgery. Note: a unique participant could have more than one surgical procedure. | Posted | Mean | Standard Deviation | [IU/dL] : [IU/kg] | Within 60 minutes prior to surgery and 15 ± 5 minutes after loading dose/rebolus, if applicable. | surgeries with IR data | surgeries with IR data |
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|
|
| 0 |
| 30 |
| 10 |
| 30 |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
|
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
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| Thrombocytosis | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
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Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of the Sponsor.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
|
| Title | Measurements |
|---|
|
| None |
|
| Title | Measurements |
|---|---|
|
| Fair |
|
| None |
|
| Title | Measurements |
|---|---|
|
| Fair |
|
| None |
|
|
| Postoperative Day 2 (N=29,21,8) |
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| Postoperative Day 3 (N=26,21,5) |
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| Postoperative Day 4 (N=24,21,3) |
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| Postoperative Day 5 (N=23,21,2) |
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| Postoperative Day 6 (N=21,20,1) |
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| Postoperative Day 7 (N=21,20,1) |
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| Postoperative Day 8 (N=19,19,0) |
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| Postoperative Day 9 (N=19,19,0) |
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| Postoperative Day 10 (N=18,18,0) |
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| Postoperative Day 11+ (N=15,15,0) |
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