Trial Outcomes & Findings for BAX 326 Surgery Study in Hemophilia B Patients (NCT NCT01507896)

NCT ID: NCT01507896

Last Updated: 2021-05-19

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 30 participants
• Primary outcome timeframe: On day of surgery
• Results posted on: 2021-05-19

Participant Flow

Enrollment was conducted at 10 clinical sites in 8 countries (Bulgaria, Czech Republic, Poland, Romania, Russia, Ukraine, Chile, Colombia).

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.

Participant milestones

Measure	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.
Overall Study STARTED	30
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	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.
Overall Study Withdrawal by Subject	1
Overall Study The surgery was denied by the sponsor.	1

Baseline Characteristics

BAX 326 Surgery Study in Hemophilia B Patients

Baseline characteristics by cohort

Measure	Treatment With BAX326 n=40 Participants 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.
Age, Continuous	39.7 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: On day of surgery

Population: 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.

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

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Intraoperative Hemostatic Efficacy Excellent	37 surgeries	20 surgeries	17 surgeries
Intraoperative Hemostatic Efficacy Good	1 surgeries	1 surgeries	0 surgeries
Intraoperative Hemostatic Efficacy Fair	0 surgeries	0 surgeries	0 surgeries
Intraoperative Hemostatic Efficacy None	0 surgeries	0 surgeries	0 surgeries

PRIMARY outcome

Timeframe: On day of surgery

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Actual Intraoperative Blood Loss	191.1 mL Standard Deviation 354.1	344.9 mL Standard Deviation 420.1	1.2 mL Standard Deviation 1.1

PRIMARY outcome

Timeframe: On day of surgery

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon Difference from predicted average blood loss	-27.0 mL Standard Deviation 158.9	-50.9 mL Standard Deviation 213.0	2.4 mL Standard Deviation 4.9
Actual Intraoperative Blood Loss Compared to Average and Maximum Blood Loss Predicted Preoperatively by the Operating Surgeon Difference from predicted maximum blood loss	128.3 mL Standard Deviation 260.8	222.0 mL Standard Deviation 323.7	12.5 mL Standard Deviation 24.5

PRIMARY outcome

Timeframe: At drain removal (from 1-3 days postoperatively)

Population: 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

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

Outcome measures

Measure	All Surgeries n=14 major surgeries with drain placed 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.	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.	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.
Postoperative Hemostatic Efficacy at Drain Removal Good	4 major surgeries with drain placed	—	—
Postoperative Hemostatic Efficacy at Drain Removal Excellent	10 major surgeries with drain placed	—	—
Postoperative Hemostatic Efficacy at Drain Removal Fair	0 major surgeries with drain placed	—	—
Postoperative Hemostatic Efficacy at Drain Removal None	0 major surgeries with drain placed	—	—

PRIMARY outcome

Timeframe: At postoperative day 3 (approximately 72 hours postoperatively)

Population: 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.

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

Outcome measures

Measure	All Surgeries n=8 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.	Major Surgeries n=7 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.	Minor Surgeries n=1 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.
Postoperative Hemostatic Efficacy at Postoperative Day 3 Fair	0 surgeries	0 surgeries	0 surgeries
Postoperative Hemostatic Efficacy at Postoperative Day 3 None	0 surgeries	0 surgeries	0 surgeries
Postoperative Hemostatic Efficacy at Postoperative Day 3 Excellent	7 surgeries	6 surgeries	1 surgeries
Postoperative Hemostatic Efficacy at Postoperative Day 3 Good	1 surgeries	1 surgeries	0 surgeries

PRIMARY outcome

Timeframe: At discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)

Population: 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.

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

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Postoperative Hemostatic Efficacy on Day of Discharge Excellent	29 surgeries	12 surgeries	17 surgeries
Postoperative Hemostatic Efficacy on Day of Discharge Good	7 surgeries	7 surgeries	0 surgeries
Postoperative Hemostatic Efficacy on Day of Discharge Fair	2 surgeries	2 surgeries	0 surgeries
Postoperative Hemostatic Efficacy on Day of Discharge None	0 surgeries	0 surgeries	0 surgeries

PRIMARY outcome

Timeframe: At drain removal (from 1-3 days postoperatively)

Population: 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.

Postoperative blood loss was based on the drainage fluid and was only assessed for participants who had a drain placed during surgery.

Outcome measures

Measure	All Surgeries n=14 surgeries with drain placed 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.	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.	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.
Actual Postoperative Blood Loss	603.6 mL Standard Deviation 388.7	—	—

PRIMARY outcome

Timeframe: At postoperative day 3 (approximately 72 hours postoperatively)

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=14 surgeries with drain placed 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.	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.	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.
Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon Difference from predicated average blood loss	-221.4 mL Standard Deviation 331.7	—	—
Actual Postoperative Blood Loss Compared to Average and Maximum Blood Loss Predicated Preoperatively by the Operating Surgeon Difference from predicted maximum blood loss	147.1 mL Standard Deviation 330.1	—	—

PRIMARY outcome

Timeframe: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Daily Weight-Adjusted Dose of BAX326 Per Participant Day of Surgery	144.8 IU/kg Standard Deviation 70.3	191.5 IU/kg Standard Deviation 50.6	87.2 IU/kg Standard Deviation 42.9
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 1	103.9 IU/kg Standard Deviation 44.6	136.7 IU/kg Standard Deviation 30.1	63.5 IU/kg Standard Deviation 18.0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 2 (N=29,21,8)	115.0 IU/kg Standard Deviation 40.2	134.2 IU/kg Standard Deviation 27.6	64.6 IU/kg Standard Deviation 16.2
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 3 (N=26,21,5)	111.6 IU/kg Standard Deviation 43.9	123.5 IU/kg Standard Deviation 39.4	61.6 IU/kg Standard Deviation 20.8
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 4 (N=24,21,3)	115.2 IU/kg Standard Deviation 63.0	123.5 IU/kg Standard Deviation 62.4	56.9 IU/kg Standard Deviation 29.3
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 5 (N=23,21,2)	104.4 IU/kg Standard Deviation 47.4	108.6 IU/kg Standard Deviation 46.6	60.4 IU/kg Standard Deviation 41.9
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 6 (N=21,20,1)	105.6 IU/kg Standard Deviation 44.0	106.6 IU/kg Standard Deviation 44.9	86.0 IU/kg Standard Deviation 0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 7 (N=21,20,1)	94.6 IU/kg Standard Deviation 46.7	96.1 IU/kg Standard Deviation 47.4	65.5 IU/kg Standard Deviation 0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 8 (N=19,19,0)	93.0 IU/kg Standard Deviation 45.8	93.0 IU/kg Standard Deviation 45.8	0 IU/kg Standard Deviation 0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 9 (N=19,19,0)	93.0 IU/kg Standard Deviation 46.9	93.0 IU/kg Standard Deviation 46.9	0 IU/kg Standard Deviation 0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 10 (N=18,18,0)	89.9 IU/kg Standard Deviation 49.7	89.9 IU/kg Standard Deviation 49.7	0 IU/kg Standard Deviation 0
Daily Weight-Adjusted Dose of BAX326 Per Participant Postoperative Day 11+ (N=15,15,0)	75.3 IU/kg Standard Deviation 44.8	75.3 IU/kg Standard Deviation 44.8	0 IU/kg Standard Deviation 0

PRIMARY outcome

Timeframe: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)

Population: 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.

Assessed for the intra- and postoperative periods.

Outcome measures

Measure	All Surgeries n=38 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.	Major Surgeries n=21 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.	Minor Surgeries n=17 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.
Total Weight-Adjusted Dose of BAX326 Per Participant Intraoperative Period	145 IU/kg Standard Deviation 70	191 IU/kg Standard Deviation 51	87 IU/kg Standard Deviation 43
Total Weight-Adjusted Dose of BAX326 Per Participant Postoperative Period	808 IU/kg Standard Deviation 766	1350 IU/kg Standard Deviation 617	138 IU/kg Standard Deviation 136

PRIMARY outcome

Timeframe: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)

Population: 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.

Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.

Outcome measures

Measure	All Surgeries n=6 surgery where blood transfusion given 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.	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.	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.
Number of Units of Blood Product Transfused Intraoperative Period	2.8 units Standard Deviation 1.2	—	—
Number of Units of Blood Product Transfused Postoperative Period	1.5 units Standard Deviation 0.7	—	—

PRIMARY outcome

Timeframe: From initiation of surgery until discharge from hospital (from 1-3 days postoperatively for minor surgery and approximately 2 weeks postoperatively for major surgery)

Population: 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.

Blood product transfusions consisted of packed red blood cells (PRBC) or fresh frozen plasma (FFP) or both.

Outcome measures

Measure	All Surgeries n=6 surgery where blood transfusion given 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.	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.	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.
Volume of Blood Product Transfused Intraoperative period	834.3 mL Standard Deviation 358.7	—	—
Volume of Blood Product Transfused Postoperative Period (2 surgeries)	414.0 mL Standard Deviation 227.7	—	—

PRIMARY outcome

Timeframe: Throughout the study period (approximately 2 years 5 months)

Population: 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.

Outcome measures

Measure	All Surgeries n=40 treatments with BAX326 before surgery 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.	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.	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.
Safety: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)	0 participants	—	—

PRIMARY outcome

Timeframe: Throughout the study period (approximately 2 years 5 months)

Population: 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.

If there was more than 2-dilution increase as compared to pre-study level at screening.

Outcome measures

Measure	All Surgeries n=40 treatments with BAX326 before surgery 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.	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.	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.
Safety: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)	0 participants	—	—

PRIMARY outcome

Timeframe: Throughout the study period (approximately 2 years 5 months)

Population: 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.

Outcome measures

Measure	All Surgeries n=40 treatments with BAX326 before surgery 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.	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.	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.
Safety: Number of Adverse Events Related to BAX326	1 adverse events	—	—

PRIMARY outcome

Timeframe: Throughout the study period (approximately 2 years 5 months)

Population: 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.

Outcome measures

Measure	All Surgeries n=40 treatments with BAX326 before surgery 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.	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.	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.
Safety: Occurence of a Thrombotic Event	0 surgeries	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 72 Hours Post-infusion Per Dose	18.48 [IU•hour (hr)/dL] : IU/kg Standard Deviation 6.43	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve Per Dose (Total AUC/Dose)	20.60 [IU•hour (hr)/dL] : IU/kg Standard Deviation 7.32	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Mean Residence Time (MRT)	27.17 hours (hr) Standard Deviation 4.03	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

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).

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL)	0.0523 dL/(kg•hr) Standard Deviation 0.0126	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion at 30 minutes

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Incremental Recovery (IR) at 30 Min	1.00 IU/dL : IU/kg Standard Deviation 0.29	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

T1/2 was determined as ln2 / λz.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)	23.60 hours (hr) Standard Deviation 3.60	—	—

PRIMARY outcome

Timeframe: Within 30 mins pre-infusion and post-infusion timepoints of 30 minutes, 6 hr, 24 hr, 48 hr and 72 hr

Population: 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.

Vss was computed as CL·MRT.

Outcome measures

Measure	All Surgeries n=12 pre-surgical PK assessments 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.	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.	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.
Pre-Surgical Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)	1.41 dL/kg Standard Deviation 0.38	—	—

PRIMARY outcome

Timeframe: Within 60 minutes prior to surgery and 15 ± 5 minutes after loading dose/rebolus, if applicable.

Population: 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.

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.

Outcome measures

Measure	All Surgeries n=36 surgeries with IR data 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.	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.	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.
Incremental Recovery (IR) at 15±5 Minutes Following Loading Dose Prior to Surgery	0.910 [IU/dL] : [IU/kg] Standard Deviation 0.1787	—	—

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Participants n=30 participants at risk All unique participants treated with BAX326 per planned surgical procedure.
Injury, poisoning and procedural complications Post procedural swelling	10.0% 3/30 • Throughout the study period (approximately 2 years 5 months)
Injury, poisoning and procedural complications Procedural pain	23.3% 7/30 • Throughout the study period (approximately 2 years 5 months)
Blood and lymphatic system disorders Haemorrhagic anaemia	10.0% 3/30 • Throughout the study period (approximately 2 years 5 months)
Blood and lymphatic system disorders Thrombocytosis	13.3% 4/30 • Throughout the study period (approximately 2 years 5 months)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER