Trial Outcomes & Findings for Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery (NCT NCT02283268)

NCT ID: NCT02283268

Last Updated: 2021-05-19

Results Overview

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intra-, and postoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intra-, and postoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intra-, and postoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 24 participants
• Primary outcome timeframe: 24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier
• Results posted on: 2021-05-19

Participant Flow

Enrollment was conducted at 14 study sites in 10 countries (USA, Australia, Taiwan, Germany, Russia, Spain, Ukraine, United Kingdom, Italy, Turkey).

A total of 24 participants were enrolled (signed informed consent) and screened. Of these, 15 participants were treated with investigational product.

Participant milestones

Measure	Recombinant Von Willebrand Factor (rVWF) Surgery participants treated with Recombinant von Willebrand Factor (rVWF)
Overall Study STARTED	15
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Recombinant Von Willebrand Factor (rVWF) Surgery participants treated with Recombinant von Willebrand Factor (rVWF)
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery

Baseline characteristics by cohort

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)
Age, Continuous	40.0 Years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier

Population: Number of participants with major, minor and oral surgery and number of participant with Von Willebrand Type 1, 2A, 2B, 2M and 3 do sum up to the overall number of participants analyzed. The full analysis data set, including all participants who received investigational product and have at least 1 hemostatic assessment, was used for analysis.

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intra-, and postoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intra-, and postoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intra-, and postoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery n=4 Participants All participants who underwent minor surgery.	Major Surgery n=10 Participants All participants who underwent major surgery.	Oral Surgery n=1 Participants All participants who underwent oral surgery.	Von Willebrand Disease Type 1 n=3 Participants All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A n=2 Participants All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B n=1 Participants All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M n=1 Participants All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 n=8 Participants All participants with von Willebrand Disease Type 3.
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) Excellent	11 Participants	4 Participants	7 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	7 Participants
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) Good	4 Participants	0 Participants	3 Participants	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) None	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 0 (at completion of surgery)

Population: For predicted blood loss the number of participants analyzed is 14 as for one participant (included in the major surgery reporting group) the predicted blood loss was not collected. The full analysis data set, including all participants who received investigational product and have at least 1 hemostatic assessment, was used for analysis.

The predicted blood loss will be estimated preoperatively by the operating surgeon based on a hemostatically normal individual of the same sex, age, stature and co-morbidities as the participant. The actual blood loss will be assessed consisting of the estimated blood loss, including into swabs, towels and suction during the procedure, per the anesthesiologist's record.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery n=4 Participants All participants who underwent minor surgery.	Major Surgery n=10 Participants All participants who underwent major surgery.	Oral Surgery n=1 Participants All participants who underwent oral surgery.	Von Willebrand Disease Type 1 n=3 Participants All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A n=2 Participants All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B n=1 Participants All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M n=1 Participants All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 n=8 Participants All participants with von Willebrand Disease Type 3.
Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon Actual blood loss	94.3 mL Standard Deviation 177.88	0.0 mL Standard Deviation 0.00	127.0 mL Standard Deviation 209.27	145.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	115.0 mL Standard Deviation 103.32	42.5 mL Standard Deviation 53.03	50.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	50.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	110.6 mL Standard Deviation 240.87
Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon Predicted blood loss	106.1 mL Standard Deviation 161.82	2.5 mL Standard Deviation 5.00	152.8 mL Standard Deviation 186.33	100.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	100.0 mL Standard Deviation 100.00	10.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	50.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	50.0 mL Standard Deviation NA No standard deviation possible as only one participant was analyzed.	134.4 mL Standard Deviation 206.46

SECONDARY outcome

Timeframe: Day 0 (at completion of surgery)

Population: Number of participants analyzed is 11, as for 3 participants the actual and the predicted blood loss was zero and for 1 participant the predicted blood loss was not collected. Therefore 'actual blood loss relative to predicted blood loss' could not be calculated. The full analysis data set was used for the analysis of this outcome measure.

Actual blood loss relative to predicted blood loss will be calculated as [Actual Blood loss (mL)] divided by [Predicted Blood Loss (mL) multiplied by 100.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery n=1 Participants All participants who underwent minor surgery.	Major Surgery n=9 Participants All participants who underwent major surgery.	Oral Surgery n=1 Participants All participants who underwent oral surgery.	Von Willebrand Disease Type 1 n=2 Participants All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A n=1 Participants All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B n=1 Participants All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M n=1 Participants All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 n=6 Participants All participants with von Willebrand Disease Type 3.
Intraoperative Actual Blood Loss Relative to Predicted Blood Loss	69.6 Percent Standard Deviation 44.77	0.0 Percent Standard Deviation NA No standard deviation possible as only one participant was analyzed.	68.9 Percent Standard Deviation 34.48	145.0 Percent Standard Deviation NA No standard deviation possible as only one participant was analyzed.	122.5 Percent Standard Deviation 31.82	50.0 Percent Standard Deviation NA No standard deviation possible as only one participant was analyzed.	100.0 Percent Standard Deviation NA No standard deviation possible as only one participant was analyzed.	100.0 Percent Standard Deviation NA No standard deviation possible as only one participant was analyzed.	45.0 Percent Standard Deviation 38.92

SECONDARY outcome

Timeframe: Day 0 (at completion of surgery)

Population: Number of participants with major, minor and oral surgery and number of participant with Von Willebrand Type 1, 2A, 2B, 2M and 3 do sum up to the overall number of participants analyzed. The full analysis data set, including all participants who received investigational product and have at least 1 hemostatic assessment, was used for analysis.

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intraoperative blood loss was less than or equal to the maximum blood loss expected for the type of procedure performed in a hemostatically normal subject (≤ 100%). Good: Intraoperative blood loss was up to 50% more than the maximum expected blood loss for the type of procedure performed in a hemostatically normal subject (101-150%) Moderate: Intraoperative blood loss was more than 50% of the maximum expected blood loss for the type of procedure performed in a hemostatically normal subject (>150%). None: Uncontrolled hemorrhage that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of clotting factor replacement regimen.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery n=4 Participants All participants who underwent minor surgery.	Major Surgery n=10 Participants All participants who underwent major surgery.	Oral Surgery n=1 Participants All participants who underwent oral surgery.	Von Willebrand Disease Type 1 n=3 Participants All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A n=2 Participants All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B n=1 Participants All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M n=1 Participants All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 n=8 Participants All participants with von Willebrand Disease Type 3.
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon Excellent	13 Participants	4 Participants	8 Participants	1 Participants	3 Participants	1 Participants	1 Participants	1 Participants	7 Participants
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon Good	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon None	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 0 (at completion of surgery)

Population: Number of participants with major, minor and oral surgery and number of participant with Von Willebrand Type 1, 2A, 2B, 2M and 3 do sum up to the overall number of participants analyzed. The full analysis data set, including all participants who received investigational product and have at least 1 hemostatic assessment, was used for analysis.

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intraoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intraoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intraoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery n=4 Participants All participants who underwent minor surgery.	Major Surgery n=10 Participants All participants who underwent major surgery.	Oral Surgery n=1 Participants All participants who underwent oral surgery.	Von Willebrand Disease Type 1 n=3 Participants All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A n=2 Participants All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B n=1 Participants All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M n=1 Participants All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 n=8 Participants All participants with von Willebrand Disease Type 3.
Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon Excellent	13 Participants	4 Participants	8 Participants	1 Participants	3 Participants	1 Participants	1 Participants	1 Participants	7 Participants
Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon Good	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon None	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Daily, from day of surgery through postoperative Day 14 (± 2 days)

Population: Number of participants analyzed is different for the time points according to individual treatment. The full analysis data set, including all participants who received investigational product and have at least 1 hemostatic assessment, was used for analysis.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 12	29.3 IU/kg Interval 20.1 to 44.2	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE intraoperative	18.1 IU/kg Interval 18.1 to 18.1	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 1	23.5 IU/kg Interval 16.9 to 47.2	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 2	42.3 IU/kg Interval 23.2 to 50.6	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 3	28.6 IU/kg Interval 20.6 to 48.9	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 4	33.9 IU/kg Interval 23.2 to 44.3	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 5	31.5 IU/kg Interval 18.8 to 47.2	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 6	23.2 IU/kg Interval 18.8 to 23.6	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 7	23.8 IU/kg Interval 23.6 to 50.8	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 8	33.9 IU/kg Interval 23.6 to 53.6	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 9	23.6 IU/kg Interval 16.3 to 53.6	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 10	23.6 IU/kg Interval 16.3 to 34.8	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 11	23.6 IU/kg Interval 16.3 to 53.6	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 13	16.3 IU/kg Interval 16.3 to 16.3	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 14	25.5 IU/kg Interval 16.3 to 34.8	—	—	—	—	—	—	—	—
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE postoperative day 15	16.3 IU/kg Interval 16.3 to 16.3	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)

Population: The safety analysis data set, including all participants who received any amount of investigational product, was used for analysis of this outcome measure.

Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) will be evaluated.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Occurrence of Adverse Events Treatment emergent Adverse Events (TEAEs)	12 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events Severe TEAEs	1 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs related to rVWF	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs related to ADVATE	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs related to both rVWF and ADVATE	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events Treatment emergent Serious Adverse Events (TESAEs)	2 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TESAEs related to rVWF	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TESAEs related to ADVATE	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TESAEs related to both rVWF and ADVATE	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs leading to discontinuation of rVWF	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs leading to discontinuation of ADVATE	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs leading to discontinuation of study	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs leading to death	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TEAEs related to study procedure	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Adverse Events TESAEs related to study procedure	0 Adverse Events	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)

Population: The safety analysis data set, including all participants who received any amount of investigational product, was used for analysis of this outcome measure.

Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) will be evaluated for thrombotic events.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Occurrence of Thrombotic Events Thrombotic TEAEs	2 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Thrombotic Events Thrombotic TESAEs	1 Adverse Events	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)

Population: The safety analysis data set, including all participants who received any amount of investigational product, was used for analysis of this outcome measure.

Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) will be evaluated for severe allergic reactions.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Occurrence of Severe Allergic Reactions (eg, Anaphylaxis) Severe allergic reaction TEAEs	0 Adverse Events	—	—	—	—	—	—	—	—
Occurrence of Severe Allergic Reactions (eg, Anaphylaxis) Severe allergic reaction TESAEs	0 Adverse Events	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).

Population: The safety analysis data set, including all participants who received any amount of investigational product, was used for analysis of this outcome measure.

Participants were treated with recombinant van Willebrand Factor (rVWF) with or without ADVATE.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII) Development of inhibitory antibodies to FVIII	0 Participants	—	—	—	—	—	—	—	—
Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII) Development of inhibitory antibodies to VWF	0 Participants	—	—	—	—	—	—	—	—
Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII) Development of total binding antibodies to VWF	1 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).

Population: The safety analysis data set, including all participants who received any amount of investigational product, was used for analysis of this outcome measure.

Participants were treated with recombinant van Willebrand Factor (rVWF) with or without ADVATE.

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) or Recombinant Furin (rFurin)	0 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. The area under the plasma concentration/time curve from 0 to 72 hours post-infusion will be computed using the linear trapezoidal rule. For the calculation of AUC(0-72h) the levels at 72 hours will be linearly interpolated/extrapolated from the 2 nearest sampling time points. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac), FVIII Coagulation Activity (FVIII:C)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) VWF:RCo	31.91 hours*IU/dL Geometric Coefficient of Variation 37.5	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) VWF:Ag	57.08 hours*IU/dL Geometric Coefficient of Variation 25.6	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) VWF:CB	63.91 hours*IU/dL Geometric Coefficient of Variation 29.4	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) VWF:Ac	54.61 hours*IU/dL Geometric Coefficient of Variation 28.1	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) FVIII:C	67.49 hours*IU/dL Geometric Coefficient of Variation 31.1	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. The area under the plasma concentration/time curve from time 0 to infinity and the area under the first moment curve from time 0 to infinity will be calculated as the sum of AUC or AUMC from time 0 to the time of last quantifiable concentration plus a tail area correction calculated as Ct/λz and Ct/λz(t+1/λz), respectively, where Ct is the last quantifiable concentration, t is the time of last quantifiable concentration and λz is the terminal or disposition rate constant. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac), FVIII Coagulation Activity (FVIII:C)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) VWF:RCo	34.43 hours*IU/dL Geometric Coefficient of Variation 43.3	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) VWF:Ag	68.87 hours*IU/dL Geometric Coefficient of Variation 31.5	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) VWF:CB	71.82 hours*IU/dL Geometric Coefficient of Variation 34.1	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) VWF:Ac	61.90 hours*IU/dL Geometric Coefficient of Variation 32.2	—	—	—	—	—	—	—	—
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) FVIII:C	75.00 hours*IU/dL Geometric Coefficient of Variation 30.9	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. Mean residence time will be calculated as area under the first moment curve from time 0 to infinity divided by the area under the curve time 0 to infinity minus T/2 where T is the duration of the infusion. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Mean Residence Time (MRT) VWF:RCo	22.69 hours Geometric Coefficient of Variation 41.3	—	—	—	—	—	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) VWF:Ag	37.92 hours Geometric Coefficient of Variation 28.4	—	—	—	—	—	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) VWF:CB	29.35 hours Geometric Coefficient of Variation 31.1	—	—	—	—	—	—	—	—
Pharmacokinetics: Mean Residence Time (MRT) VWF:Ac	29.75 hours Geometric Coefficient of Variation 28.6	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. Clearance will be calculated as dose (IU/kg) divided by the area under the curve time 0 to infinity. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Clearance (CL) VWF:RCo	0.02904 dL/hour/kg Geometric Coefficient of Variation 43.3	—	—	—	—	—	—	—	—
Pharmacokinetics: Clearance (CL) VWF:Ag	0.01452 dL/hour/kg Geometric Coefficient of Variation 31.5	—	—	—	—	—	—	—	—
Pharmacokinetics: Clearance (CL) VWF:CB	0.01392 dL/hour/kg Geometric Coefficient of Variation 34.1	—	—	—	—	—	—	—	—
Pharmacokinetics: Clearance (CL) VWF:Ac	0.01616 dL/hour/kg Geometric Coefficient of Variation 32.2	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. Incremental recovery will be calculated as (Cmax minus Cpreinfusion) divided by the dose (IU/kg) where kg refers to the body weight at the time of dosing and Cmax is the observed maximum concentration before correction for pre-infusion values. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Incremental Recovery (IR) VWF:RCo	1.961 IU/dL Standard Deviation 0.45445	—	—	—	—	—	—	—	—
Pharmacokinetics: Incremental Recovery (IR) VWF:Ag	1.991 IU/dL Standard Deviation 0.38395	—	—	—	—	—	—	—	—
Pharmacokinetics: Incremental Recovery (IR) VWF:CB	2.780 IU/dL Standard Deviation 0.56640	—	—	—	—	—	—	—	—
Pharmacokinetics: Incremental Recovery (IR) VWF:Ac	2.635 IU/dL Standard Deviation 0.38050	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. Terminal or disposition half-life (T1/2) will be calculated as ln2/λz where λz is the terminal elimination rate constant as calculated in WinNonlin NCA using at least three quantifiable concentrations. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Elimination Phase Half-life (T1/2) VWF:RCo	16.52 hours Geometric Coefficient of Variation 42.7	—	—	—	—	—	—	—	—
Pharmacokinetics: Elimination Phase Half-life (T1/2) VWF:Ag	26.88 hours Geometric Coefficient of Variation 26.5	—	—	—	—	—	—	—	—
Pharmacokinetics: Elimination Phase Half-life (T1/2) VWF:CB	21.07 hours Geometric Coefficient of Variation 33.2	—	—	—	—	—	—	—	—
Pharmacokinetics: Elimination Phase Half-life (T1/2) VWF:Ac	22.19 hours Geometric Coefficient of Variation 28.5	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The PK analysis data set, including all participants who underwent PK assessment with data collected at the relevant time points, was used for analysis of this outcome measure.

This assessment is only required for subjects undergoing major surgery. Subjects will receive a PK infusion at a dose of 50±5 IU/kg rVWF:RCo within 42 days prior to surgery. Vss will be calculated as the clearance multiplied with the mean residence time. PK analysis was performed for the following analytes: VWF Ristocetin Cofactor Activity (VWF:RCo), VWF Antigen Activity (VWF:Ag), VWF Collagen Binding Activity (VWF:CB), VWF Activity Measured INNOVANCE VWF Ac Assay (VWF:Ac)

Outcome measures

Measure	Recombinant Von Willebrand Factor (rVWF) n=11 Participants Surgery participants treated with Recombinant von Willebrand Factor (rVWF)	Minor Surgery All participants who underwent minor surgery.	Major Surgery All participants who underwent major surgery.	Oral Surgery All participants who underwent oral surgery.	Von Willebrand Disease Type 1 All participants with von Willebrand Disease Type 1.	Von Willebrand Disease Type 2A All participants with von Willebrand Disease Type 2A.	Von Willebrand Disease Type 2B All participants with von Willebrand Disease Type 2B.	Von Willebrand Disease Type 2M All participants with von Willebrand Disease Type 2M.	Von Willebrand Disease Type 3 All participants with von Willebrand Disease Type 3.
Pharmacokinetics: Volume of Distribution at Steady State (Vss) VWF:RCo	0.6591 dL/kg Geometric Coefficient of Variation 28.8	—	—	—	—	—	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) VWF:Ag	0.5506 dL/kg Geometric Coefficient of Variation 18.4	—	—	—	—	—	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) VWF:CB	0.4086 dL/kg Geometric Coefficient of Variation 24.0	—	—	—	—	—	—	—	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) VWF:Ac	0.4806 dL/kg Geometric Coefficient of Variation 21.5	—	—	—	—	—	—	—	—

Adverse Events

Recombinant Von Willebrand Factor (rVWF)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 participants at risk Surgery participants treated with Recombinant von Willebrand Factor (rVWF)
Infections and infestations Diverticulitis	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Vascular disorders Deep vein thrombosis	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.

Other adverse events

Measure	Recombinant Von Willebrand Factor (rVWF) n=15 participants at risk Surgery participants treated with Recombinant von Willebrand Factor (rVWF)
Skin and subcutaneous tissue disorders Acne	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Skin and subcutaneous tissue disorders Dry skin	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Blood and lymphatic system disorders Iron deficiency anaemia	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
General disorders Peripheral swelling	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Infections and infestations Nasopharyngitis	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Musculoskeletal and connective tissue disorders Joint swelling	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Nervous system disorders Headache	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Reproductive system and breast disorders Pelvic pain	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.
Vascular disorders Deep vein thrombosis	6.7% 1/15 • Number of events 1 • Throughout the study period (from the first exposure to investigational product until study completion or discontinuation date). Total study duration: 1 year and 3 months. Per participant: up to 58 days.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until completion of the multicenter publication or one year after the conclusion of the study at all sites. Baxalta requires a review of results communication (e.g. for confidential information) \>= 30 days prior to submission. Baxalta may request an additional delay of \<= 6 months (e.g. for intellectual property protection).
• Publication restrictions are in place

Restriction type: OTHER