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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01410227




Registration number
NCT01410227
Ethics application status
Date submitted
4/08/2011
Date registered
5/08/2011

Titles & IDs
Public title
Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)
Scientific title
A Phase 3 Clinical Study to Determine the Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor : Recombinant Factor VIII (rVWF:rFVIII) and rVWF in the Treatment of Bleeding Episodes in Subjects Diagnosed With Von Willebrand Disease
Secondary ID [1] 0 0
2010-024108-84
Secondary ID [2] 0 0
071001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Von Willebrand Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Recombinant von Willebrand factor (rVWF)
Treatment: Drugs - Placebo
Treatment: Other - Recombinant factor VIIII (rFVIII)

Experimental: PK 80 Arm (minimum of 22 subjects with severe VWD) - PK assessment (80 IU/kg rVWF) + 12-month treatment period

Experimental: PK 50 Arm (14 subjects with type 3 VWD) - Two single-blinded PK assessments (50 IU/kg rVWF + rFVIII/placebo) + 12-month treatment period

Experimental: PK 50 Only Arm (minimum of 7 subjects with type 3 VWD) - PK assessment (50 IU/kg rVWF) only, no treatment of bleeding episodes

Experimental: Treatment Only (up to 7 subjects independent of VWD subtype) - Treatment of bleeding episodes for a total of 12 months


Treatment: Other: Recombinant von Willebrand factor (rVWF)
Intravenous administration

Treatment: Drugs: Placebo
Syringe supplied with physiologic saline solution for infusion

Treatment: Other: Recombinant factor VIIII (rFVIII)
Intravenous administration

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Treatment Success for Treated Bleeding Episodes
Timepoint [1] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [1] 0 0
Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good"
Timepoint [1] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [2] 0 0
Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good", Excluding Gastrointestinal Bleeds
Timepoint [2] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [3] 0 0
Number of Infusions of rVWF:rFVIII and/or rVWF Per Bleeding Episode
Timepoint [3] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [4] 0 0
Number of Units of rVWF:rFVIII and/or rVWF Per Bleeding Episode
Timepoint [4] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [5] 0 0
Percentage of Participants Who Develop Inhibitory Antibodies to FVIII
Timepoint [5] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [6] 0 0
Percentage of Participants Who Develop Inhibitory Antibodies to VWF
Timepoint [6] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [7] 0 0
Percentage of Participants Who Develop Binding Antibodies to VWF
Timepoint [7] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [8] 0 0
Percentage of Participants Who Develop Binding Antibodies to CHO
Timepoint [8] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [9] 0 0
Percentage of Participants Who Develop Binding Antibodies to rFurin
Timepoint [9] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [10] 0 0
Percentage of Participants Who Develop Binding Antibodies to Mouse Immunoglobulin
Timepoint [10] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [11] 0 0
Percentage of Participants Who Had an Occurrence of Thrombotic Events
Timepoint [11] 0 0
After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [12] 0 0
Number of Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Timepoint [12] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [13] 0 0
Number of Participants With Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Timepoint [13] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [14] 0 0
Number of Adverse Events by Infusion Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Timepoint [14] 0 0
For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcome [15] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:RCo
Timepoint [15] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [16] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
Timepoint [16] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [17] 0 0
PK50 - Mean Residence Time of VWF:RCo
Timepoint [17] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [18] 0 0
PK50 - Clearance of VWF:RCo
Timepoint [18] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [19] 0 0
PK50 - Incremental Recovery of VWF:RCo
Timepoint [19] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [20] 0 0
PK50 - Elimination Phase Half-Life of VWF:Co
Timepoint [20] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [21] 0 0
PK50 - Volume of Distribution at Steady State of VWF:RCo
Timepoint [21] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [22] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:Ag
Timepoint [22] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [23] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
Timepoint [23] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout
Secondary outcome [24] 0 0
PK50 - Mean Residence Time of VWF:Ag
Timepoint [24] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [25] 0 0
PK50 - Clearance of VWF:Ag
Timepoint [25] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [26] 0 0
PK50 - Incremental Recovery of VWF:Ag
Timepoint [26] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [27] 0 0
PK50 - Elimination Phase Half-Life of VWF:Ag
Timepoint [27] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [28] 0 0
PK50 - Volume of Distribution at Steady State of VWF:Ag
Timepoint [28] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [29] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:CB
Timepoint [29] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [30] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
Timepoint [30] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [31] 0 0
PK50 - Mean Residence Time of VWF:CB
Timepoint [31] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [32] 0 0
PK50 - Clearance of VWF:CB
Timepoint [32] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [33] 0 0
PK50 - Incremental Recovery of VWF:CB
Timepoint [33] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [34] 0 0
PK50 - Elimination Phase Half-Life of VWF:CB
Timepoint [34] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [35] 0 0
PK50 - Volume of Distribution at Steady State of VWF:CB
Timepoint [35] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [36] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of FVIII:C
Timepoint [36] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [37] 0 0
PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
Timepoint [37] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [38] 0 0
PK50 - Mean Residence Time of FVIII:C
Timepoint [38] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [39] 0 0
PK50 - Clearance of FVIII:C
Timepoint [39] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [40] 0 0
PK50 - Incremental Recovery of FVIII:C
Timepoint [40] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [41] 0 0
PK50 - Elimination Phase Half-Life of FVIII:C
Timepoint [41] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [42] 0 0
PK50 - Volume of Distribution at Steady State of FVIII:C
Timepoint [42] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [43] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:RCo
Timepoint [43] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [44] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
Timepoint [44] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [45] 0 0
PK80 - Mean Residence Time of VWF:RCo
Timepoint [45] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [46] 0 0
PK80 - Clearance of VWF:RCo
Timepoint [46] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [47] 0 0
PK80 - Incremental Recovery of VWF:RCo
Timepoint [47] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [48] 0 0
PK80 - Elimination Phase Half-Life of VWF:Co
Timepoint [48] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [49] 0 0
PK80 - Volume of Distribution at Steady State of VWF:RCo
Timepoint [49] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [50] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:Ag
Timepoint [50] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [51] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
Timepoint [51] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [52] 0 0
PK80 - Mean Residence Time of VWF:Ag
Timepoint [52] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [53] 0 0
PK80 - Clearance of VWF:Ag
Timepoint [53] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [54] 0 0
PK80 - Incremental Recovery of VWF:Ag
Timepoint [54] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [55] 0 0
PK80 - Elimination Phase Half-Life of VWF:Ag
Timepoint [55] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [56] 0 0
PK80 - Volume of Distribution at Steady State of VWF:Ag
Timepoint [56] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [57] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of VWF:CB
Timepoint [57] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [58] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
Timepoint [58] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [59] 0 0
PK80 - Mean Residence Time of VWF:CB
Timepoint [59] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [60] 0 0
PK80 - Clearance of VWF:CB
Timepoint [60] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [61] 0 0
PK80 - Incremental Recovery of VWF:CB
Timepoint [61] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [62] 0 0
PK80 - Elimination Phase Half-Life of VWF:CB
Timepoint [62] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [63] 0 0
PK80 - Volume of Distribution at Steady State of VWF:CB
Timepoint [63] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [64] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-8/Dose) of FVIII:C
Timepoint [64] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [65] 0 0
PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
Timepoint [65] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Secondary outcome [66] 0 0
PK80- Ratio of Intra-participant PK of VWF:RCo, VWF:Ag and VWF:CB at Baseline and After 6 Months
Timepoint [66] 0 0
PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.

Eligibility
Key inclusion criteria
* Participant has been diagnosed with:

1. Type 1 (Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) < 20 IU/dL) or,
2. Type 2A (VWF:RCo < 20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII activity (FVIII:C) <10% and historically documented genetics), Type 2M or,
3. Type 3 ( Von Willebrand factor antigen (VWF:Ag) = 3 IU/dL) or,
4. Severe Von Willebrand disease (VWD) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding
* Participant, who participates in the treatment for bleeding episodes, has had a minimum of 1 documented bleed (medical history) requiring VWF coagulation factor replacement therapy during the previous 12 months prior to enrollment.
* Participant has a Karnofsky score = 60%
* Participant is at least 18 and not older than 65 years of age at enrollment
* If female of childbearing potential, participant presents with a negative pregnancy test
* Participant agrees to employ adequate birth control measures for the duration of the study
* Participant is willing and able to comply with the requirements of the protocol
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or elevated PT/international normalized ratio [INR] >1.4).
* Participant has a documented history of a VWF:RCo half-life of <6 hours.
* Participant has a history or presence of a VWF inhibitor at screening.
* Participant has a history or presence of a factor VIII (FVIII) inhibitor with a titer =0.4 BU (by Nijmegen assay) or = 0.6 BU (by Bethesda assay).
* Participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
* Participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
* Participant has a medical history of a thromboembolic event.
* Participant is HIV positive with an absolute CD4 count <200/mm3.
* Participant has been diagnosed with cardiovascular disease (New York Heart Association [NYHA] classes 1-4.
* Participant has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, non-seasonal asthma) at screening.
* Participant has been diagnosed with significant liver disease as evidenced by any of the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices).
* Participant has been diagnosed with renal disease, with a serum creatinine level =2 mg/dL.
* In the judgment of the investigator, the participant has another clinically significant concomitant disease (eg, uncontrolled hypertension) that may pose additional risks for the participant.
* Participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment
* Participant is pregnant or lactating at the time of enrollment.
* Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study.
* Participant has a history of drug or alcohol abuse within the 2 years prior to enrollment.
* Participant has a progressive fatal disease and/or life expectancy of less than 3 months.
* Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
* Participant suffers from a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
* Participant is in prison or compulsory detention by regulatory and/or juridical order

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6847 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Austria
State/province [10] 0 0
Vienna
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sofia
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Varna
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Duisburg
Country [18] 0 0
Germany
State/province [18] 0 0
Mainz
Country [19] 0 0
India
State/province [19] 0 0
Pune
Country [20] 0 0
India
State/province [20] 0 0
Vellore
Country [21] 0 0
Italy
State/province [21] 0 0
Florence
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Padova
Country [24] 0 0
Italy
State/province [24] 0 0
Roma
Country [25] 0 0
Italy
State/province [25] 0 0
Vicenza
Country [26] 0 0
Japan
State/province [26] 0 0
Nagoya
Country [27] 0 0
Japan
State/province [27] 0 0
Tokyo
Country [28] 0 0
Netherlands
State/province [28] 0 0
Rotterdam
Country [29] 0 0
Netherlands
State/province [29] 0 0
Utrecht
Country [30] 0 0
Poland
State/province [30] 0 0
Gdansk
Country [31] 0 0
Poland
State/province [31] 0 0
Krakow
Country [32] 0 0
Poland
State/province [32] 0 0
Warsaw
Country [33] 0 0
Poland
State/province [33] 0 0
Wroclaw
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Ekaterinburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Kirov
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Krasnoyarsk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
St. Petersburg
Country [38] 0 0
Spain
State/province [38] 0 0
Galicia
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Palma de Mallorca
Country [41] 0 0
Spain
State/province [41] 0 0
Santander
Country [42] 0 0
Sweden
State/province [42] 0 0
Gothenburg
Country [43] 0 0
Sweden
State/province [43] 0 0
Malmö
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Baxalta now part of Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Gill JC, Castaman G, Windyga J, Kouides P, Ragni M... [More Details]