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Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)

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ClinicalTrials.gov Identifier: NCT01410227
Recruitment Status : Completed
First Posted : August 5, 2011
Results First Posted : April 21, 2016
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Von Willebrand Disease
Interventions Biological: Recombinant von Willebrand factor (rVWF)
Drug: Placebo
Biological: Recombinant factor VIIII (rFVIII)
Enrollment 49
Recruitment Details Participants were enrolled (signed informed consent) from 30 sites in 15 countries.
Pre-assignment Details 49 participants provided informed consent and were screened for the study, of which 37 were exposed to study product. Reasons for discontinuation were 6 screen failures, consent withdrawn by 3 participants, 1 physician decision, 1 participant received high doses of rFVIII for oral procedure and arm for which 1 participant was eligible was closed.
Arm/Group Title Arm 1: PK50 + Treatment Arm 2: PK50 Only Arm 3: PK80 + Treatment Arm 4: Treatment Only
Hide Arm/Group Description In Part A, (pharmacokinetic [PK] assessment followed by on-demand treatment for bleeding episodes [BEs] for 6 months) participants were initially infused either with 50 IU/kg recombinant von Willebrand Factor:von Willebrand Ristocetin cofactor (VWF:RCo rVWF) [rVWF] administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline. Participants then crossed over to the alternate infusion after washout (PK). For on-demand treatment, participants received study product [VWF:rFVIII or rVWF], where BEs were initially treated with rVWF:rFVIII and subsequently with rVWF with or without rFVIII, based on FVIII levels (dose based on previous FVIII levels or if not available from the individual participant's PK data at discretion of investigator). In part, B participants continued to receive on-demand treatment for BEs with study product [VWF:rFVIII or rVWF] for a further 6 months. In Part A, (pharmacokinetic [PK] assessment followed by on-demand treatment for bleeding episodes [BEs] for 6 months) participants were initially infused either with 50 IU/kg recombinant von Willebrand Factor:von Willebrand Ristocetin cofactor (VWF:RCo rVWF) [rVWF] administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline. Participants then crossed over to the alternate infusion after washout (PK). For on-demand treatment, participants received study product [VWF:rFVIII or rVWF], where BEs were initially treated with rVWF:rFVIII and subsequently with rVWF with or without rFVIII, based on FVIII levels (dose based on previous FVIII levels or if not available from the individual participant's PK data at discretion of investigator). Participants then exited the study or could opt to sign informed consent to move to Arm 1 receive treatment for bleeding episodes with study product. In Part A, participants initially underwent a first PK assessment of an infusion of 80 IU/kg recombinant von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF]. After the first PK assessment participants received on demand treatment for bleeding episodes (BEs) with study product [VWF:rFVIII or rVWF], where BEs were initially treated with rVWF:rFVIII and subsequently with rWVF with or without rFVIII, based on FVIII levels. If FVIII levels not available, the individual participant's PK data was used to determine rFVIII dose at discretion of investigator. Participants received on-demand treatment for 6 months after the first study product infusion. After 6 months participants underwent a second PK assessment of an infusion of 80 IU/kg rVWF. In part B, participants continued to receive on-demand treatment for BEs with study product [VWF:rFVIII or rVWF] for a further 6 months. In Part A, participants received on-demand treatment for bleeding episodes (BEs) with study product (recombinant von Willebrand Factor [rVWF] administered together with recombinant Factor VIII [rFVIII] (rVWF:rFVIII) or rVWF alone), where BEs were initially treated with rVWF:rFVIII and subsequently with rVWF with or without rFVIII, based on FVIII levels. If not available, the individual participant's PK data was used to determine rFVIII dose at discretion of investigator. Participants received on-demand treatment for 6 months after the first study product infusion. In part, B participants continued to receive on-demand treatment for BEs with study product [VWF:rFVIII or rVWF] for a further 6 months. No pharmacokinetic (PK) assessments were conducted in this arm.
Period Title: Overall Study
Started 8 8 15 6
Completed 4 8 13 5
Not Completed 4 0 2 1
Reason Not Completed
Adverse Event             1             0             0             0
Withdrawal by Subject             3             0             1             0
Pregnancy             0             0             0             1
Met Excl. Criteria After Starting Study             0             0             1             0
Arm/Group Title All Subjects Treated With Study Product
Hide Arm/Group Description All subjects treated with study product
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
Baseline consists of all participants in study [N=37] so is a total of the four arms described in Participant Flow (Arm 1: PK50 + Treatment [N=8]; Arm 2: PK50 Only [N=8]; Arm 3: PK80 + Treatment [N=15]; Arm 4: Treatment Only [N=6]).
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
37
(18 to 64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
20
  54.1%
Male
17
  45.9%
1.Primary Outcome
Title Percentage of Participants With Treatment Success for Treated Bleeding Episodes
Hide Description Treatment success was defined as the extent of control of bleeding episodes (BEs) using a mean efficacy rating score of <2.5 for a participant’s BEs treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) during the study period. Scores used: Excellent = 1 - actual infusions ≤ estimated number of infusions required to treat BE; no additional VWF required (all BEs); Good = 2 - >1-2 infusions (minor/moderate BEs) or <1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs); Moderate = 3 ≥ 3 infusions (minor/moderate BEs) or ≥ 1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs); None = 4 - severe uncontrolled bleeding or intensity of bleeding not changed; additional VWF required. Included participants with available primary efficacy rating (prospective-excluding gastrointestinal bleeds) in the Full Analysis Set.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Comprises of participants treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) for whom at least one efficacy rating scale was available.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percent of participants
100.0
(84.7 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Full Analysis Set
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The null hypothesis of the rate of subjects with a treatment success of <= 0.65 (H0: p <= 0.65) versus an alternative hypothesis of > 0.65 (HA: p > 0.65) was tested at the 5% one-sided level of significance. The proportion of subjects with treatment success under the alternative hypothesis was expected to be approximately 0.90. If 20 subjects were treated, the study provided 86% power to reject the null hypothesis.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Clopper-Pearson
Comments [Not Specified]
Method of Estimation Estimation Parameter Clopper-Pearson
Estimated Value 100
Confidence Interval (2-Sided) 90%
84.7 to 100
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good"
Hide Description Efficacy ratings "excellent" or "good" for the control of bleeding episodes (BEs) with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) are defined as follows: Excellent - actual infusions ≤ estimated number of infusions required to treat BE; no additional von Willebrand Factor (VWF) required (all BEs); Good - >1-2 infusions (minor/moderate BEs) or <1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs). The data set included prospectively estimated BEs treated with study product with an available efficacy rating from participants in the Full Analysis Set
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Comprised of participants treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) for whom at least one efficacy rating scale was available.
Overall Number of Participants Analyzed 22
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
130
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percent of bleeding episodes
100.0
(97.7 to 100.0)
3.Secondary Outcome
Title Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good", Excluding Gastrointestinal Bleeds
Hide Description Efficacy ratings of "excellent" or "good" for the control of bleeding episodes (BEs) with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) are defined as follows: Excellent - actual infusions ≤ estimated number of infusions required to treat BE; no additional von Willebrand Factor (VWF) required (all BEs); Good - >1-2 infusions (minor/moderate BEs) or <1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs). The data set included prospectively estimated BEs excluding gastrointestinal (GI) bleeds treated with study product with an available efficacy rating from participants in the Full Analysis Set.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Comprised of participants treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) for whom at least one efficacy rating scale was available.
Overall Number of Participants Analyzed 22
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
126
Geometric Mean (90% Confidence Interval)
Unit of Measure: Percent of bleeding episodes
100.0
(97.7 to 100.0)
4.Secondary Outcome
Title Number of Infusions of rVWF:rFVIII and/or rVWF Per Bleeding Episode
Hide Description The actual number of infusions of recombinant von Willebrand factor:recombinant factor VIII (rVWF:rFVIII) and/or rVWF required to treat a bleeding episode (BE). BEs were to be initially treated with an infusion of rVWF:rFVIII and subsequently with rVWF with or without rFVIII, based on FVIII levels, if available. In cases, where no FVIII levels were available, the individual participant's PK data was used to determine the rFVIII dose. The data set included prospectively estimated BEs treated with study product with an available efficacy rating from participants in the Full Analysis Set.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Comprised of participants treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) for whom at least one efficacy rating scale was available.
Overall Number of Participants Analyzed 22
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
192
Median (90% Confidence Interval)
Unit of Measure: Number of infusions
1.0
(1.0 to 1.0)
5.Secondary Outcome
Title Number of Units of rVWF:rFVIII and/or rVWF Per Bleeding Episode
Hide Description The number of units is provided as the actual dose [IU/kg] of recombinant von Willebrand factor:recombinant factor VIII (rVWF:rFVIII) and/or rVWF required to treat a bleeding episode (BE). BEs were to be initially treated with an infusion of rVWF:rFVIII and subsequently with rVWF with or without rFVIII, based on FVIII levels, if available. In cases, where no FVIII levels were available, the individual participant’s PK data was used to determine the rFVIII dose. The data set included prospectively estimated BEs treated with study product of known lot number with an available efficacy rating from participants in the Full Analysis Set.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Comprised of participants treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) for whom at least one efficacy rating scale was available.
Overall Number of Participants Analyzed 22
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
174
Median (90% Confidence Interval)
Unit of Measure: IU/kg
48.2
(43.9 to 50.2)
6.Secondary Outcome
Title Percentage of Participants Who Develop Inhibitory Antibodies to FVIII
Hide Description Development of neutralizing antibodies (inhibitors) to factor VIII (FVIII) was assessed by the Nijmegen modification of the Bethesda assay. Positive FVIII inhibitor tests were defined as ≥ 0.4 Bethesda units/mL (BU/mL) by the Nijmegen-modified Bethesda assay that is confirmed by a second test performed on an independent sample obtained 2-4 weeks following the first test. Category title includes number of participants [N] who provided data for the category.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 0
During 1st treatment until study end [N=27] 0
At final study visit [N=24] 0
7.Secondary Outcome
Title Percentage of Participants Who Develop Inhibitory Antibodies to VWF
Hide Description Neutralizing antibodies (inhibitors) to Von Willebrand Factor Ristocetin cofactor (VWF:RCo), VWF collagen binding (VWF:CB) and VWF Factor VIII binding (VWF:FVIIIB) activities were measured using Nijmegen modification of the Bethesda assay. One Bethesda Unit (BU) is thereby defined as the amount of inhibitor that decreased the measured activity in the assays to 50% of that of the negative control samples. The assays were validated using human plasma samples from two type 3 VWD patients with low (1-2 BU/mL) and high (~10 BU/mL) titer inhibitors and plasma samples from non-human primates immunized with human rVWF (>100 BU/mL). Category title includes number of participants [N] who provided data for the category.
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 0
During 1st treatment until study end [N=27] 0
At final study visit [N=24] 0
8.Secondary Outcome
Title Percentage of Participants Who Develop Binding Antibodies to VWF
Hide Description The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Category title includes number of participants [N] who provided data for the category.
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 0
During 1st treatment until study end [N=28] 0
At final study visit [N=24] 0
9.Secondary Outcome
Title Percentage of Participants Who Develop Binding Antibodies to CHO
Hide Description The presence of total binding anti-CHO antibodies was determined by measuring total immunoglobulin (Ig) antibodies (IgG, IgA, IgM) against Chinese Hamster Ovary (CHO) protein using an enzyme-linked immunosorbent assay (ELISA). Category title includes number of participants [N] who provided data for the category.
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 0
During 1st treatment until study end [N=28] 0
At final study visit [N=24] 0
10.Secondary Outcome
Title Percentage of Participants Who Develop Binding Antibodies to rFurin
Hide Description The presence of total binding anti-rFurin antibodies was determined by measuring total immunoglobulin (Ig) antibodies (IgG, IgA, IgM) against rFurin protein using an enzyme-linked immunosorbent assay (ELISA). Category title includes number of participants [N] who provided data for the category.
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 0
During 1st treatment until study end [N=28] 0
At final study visit [N=24] 0
11.Secondary Outcome
Title Percentage of Participants Who Develop Binding Antibodies to Mouse Immunoglobulin
Hide Description The presence of total binding anti-Murine immunoglobulin (IgG) antibodies was determined using an enzyme-linked immunosorbent assay (ELISA). Category title includes number of participants [N] who provided data for the category.
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
Before 1st treatment with study product [N=37] 2.8
During 1st treatment until study end [N=28] 0
At final study visit [N=24] 0
12.Secondary Outcome
Title Percentage of Participants Who Had an Occurrence of Thrombotic Events
Hide Description [Not Specified]
Time Frame After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Percent of participants
0
13.Secondary Outcome
Title Number of Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Hide Description Adverse Events (AEs) related to study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) are described. Only laboratory parameters (hematology and clinical chemistry) and vital signs (physical examination, ECG) with clinically significant findings that are recorded as AEs are included. Categories presented as Severity-System Organ Class-Preferred Term Seriousness: serious adverse event (SAE); non serious adverse event (nsAE) System Organ Class: Cardiac disorders (CARD); General disorders and administration site conditions (GEN); Investigations (INV); Nervous system disorders (NERV); Skin and subcutaneous tissue disorders (SKN); Vascular disorders (VAS). Category title includes number of AEs [N] for the category.
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Overall Number of Units Analyzed
Type of Units Analyzed: Adverse Events
125
Measure Type: Number
Unit of Measure: Number of Adverse Events
SAE-GEN-Chest discomfort [N=1] 1
SAE-INV-Heart rate increased [N=1] 1
nsAE-CARD-Tachycardia [N=1] 1
nsAE-GEN-Infusion site paraesthesia [N=1] 1
nsAE-INV-ECG T wave inversion [N=1] 1
nsAE-NERV-Dysgeusia [N=1] 1
nsAE-SKN-Pruritus generalized [N=1] 1
nsAE-VAS-Hot flush [N=1] 1
14.Secondary Outcome
Title Number of Participants With Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Hide Description Number of participants with Adverse Events (AEs) related to study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) are described. Only laboratory parameters (hematology and clinical chemistry) and vital signs (physical examination, ECG) with clinically significant findings that are recorded as AEs are included. Categories presented as Severity-System Organ Class-Preferred Term Seriousness: serious adverse event (SAE); non serious adverse event (nsAE) System Organ Class: Cardiac disorders (CARD); General disorders and administration site conditions (GEN); Investigations (INV); Nervous system disorders (NERV); Skin and subcutaneous tissue disorders (SKN); Vascular disorders (VAS).
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: Number of participants
SAE-GEN-Chest discomfort 1
SAE-INV-Heart rate increased 1
nsAE-CARD-Tachycardia 1
nsAE-GEN-Infusion site paraesthesia 1
nsAE-INV-ECG T wave inversion 1
nsAE-NERV-Dysgeusia 1
nsAE-SKN-Pruritus generalized 1
nsAE-VAS-Hot flush 1
15.Secondary Outcome
Title Number of Adverse Events by Infusion Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
Hide Description Adverse Events (AEs) by infusion related to study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) are described. Only laboratory parameters (hematology and clinical chemistry) and vital signs (physical examination, ECG) with clinically significant findings that are recorded as AEs are included. Categories presented as Severity-System Organ Class-Preferred Term Seriousness: serious adverse event (SAE); non serious adverse event (nsAE) System Organ Class: Cardiac disorders (CARD); General disorders and administration site conditions (GEN); Investigations (INV); Nervous system disorders (NERV); Skin and subcutaneous tissue disorders (SKN); Vascular disorders (VAS).
Time Frame For 12 months after first infusion of rVWF:rFVIII or rVWF
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description:
Comprised of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
Overall Number of Participants Analyzed 37
Overall Number of Units Analyzed
Type of Units Analyzed: Infusions
318
Measure Type: Number
Unit of Measure: Number of Adverse Events
SAE-GEN-Chest discomfort 1
SAE-INV-Heart rate increased 1
nsAE-CARD-Tachycardia 1
nsAE-GEN-Infusion site paraesthesia 1
nsAE-INV-ECG T wave inversion 1
nsAE-NERV-Dysgeusia 1
nsAE-SKN-Pruritus generalized 1
nsAE-VAS-Hot flush 1
16.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for subjects in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total of participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
32.4
(27.5 to 40.1)
rVWF [N=14]
32.7
(29.0 to 47.8)
17.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
31.6
(27.3 to 37.3)
rVWF [N=14]
31.3
(28.4 to 43.7)
18.Secondary Outcome
Title PK50 - Mean Residence Time of VWF:RCo
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
25.2
(20.0 to 30.1)
rVWF [N=14]
26.7
(22.7 to 36.0)
19.Secondary Outcome
Title PK50 - Clearance of VWF:RCo
Hide Description Clearance (CL) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
rVWF:rFVIII [N=16]
0.031
(0.025 to 0.041)
rVWF [N=14]
0.031
(0.021 to 0.035)
20.Secondary Outcome
Title PK50 - Incremental Recovery of VWF:RCo
Hide Description Incremental Recovery (IR) at the maximum plasma concentration of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
1.8
(1.6 to 2.4)
rVWF [N=14]
1.8
(1.5 to 2.2)
21.Secondary Outcome
Title PK50 - Elimination Phase Half-Life of VWF:Co
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant FVIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
16.6
(14.7 to 20.4)
rVWF [N=14]
19.4
(15.5 to 31.3)
22.Secondary Outcome
Title PK50 - Volume of Distribution at Steady State of VWF:RCo
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg
rVWF:rFVIII [N=16]
0.70
(0.66 to 0.93)
rVWF [N=14]
0.83
(0.70 to 0.97)
23.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
67.8
(55.1 to 81.7)
rVWF [N=14]
67.1
(55.6 to 80.5)
24.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
62.1
(52.8 to 74.9)
rVWF [N=14]
62.2
(54.7 to 74.5)
25.Secondary Outcome
Title PK50 - Mean Residence Time of VWF:Ag
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
32.1
(29.8 to 41.1)
rVWF [N=14]
34.3
(30.4 to 41.4)
26.Secondary Outcome
Title PK50 - Clearance of VWF:Ag
Hide Description Clearance (CL) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
rVWF:rFVIII [N=16]
0.015
(0.013 to 0.018)
rVWF [N=14]
0.015
(0.013 to 0.018)
27.Secondary Outcome
Title PK50 - Incremental Recovery of VWF:Ag
Hide Description Incremental Recovery (IR) at the maximum plasma concentration of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
2.3
(2.0 to 2.5)
rVWF [N=14]
2.2
(1.9 to 2.5)
28.Secondary Outcome
Title PK50 - Elimination Phase Half-Life of VWF:Ag
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant FVIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
21.8
(19.5 to 27.2)
rVWF [N=14]
25.2
(21.9 to 30.3)
29.Secondary Outcome
Title PK50 - Volume of Distribution at Steady State of VWF:Ag
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg
rVWF:rFVIII [N=16]
0.50
(0.45 to 0.56)
rVWF [N=14]
0.49
(0.45 to 0.58)
30.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
80.1
(68.4 to 95.0)
rVWF [N=14]
81.3
(71.2 to 99.8)
31.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
78.7
(66.5 to 90.5)
rVWF [N=14]
75.1
(69.2 to 97.0)
32.Secondary Outcome
Title PK50 - Mean Residence Time of VWF:CB
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
27.5
(22.7 to 32.1)
rVWF [N=14]
26.1
(25.1 to 33.2)
33.Secondary Outcome
Title PK50 - Clearance of VWF:CB
Hide Description Clearance (CL) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
rVWF:rFVIII [N=16]
0.012
(0.011 to 0.015)
rVWF [N=14]
0.012
(0.011 to 0.015)
34.Secondary Outcome
Title PK50 - Incremental Recovery of VWF:CB
Hide Description Incremental Recovery (IR) at the maximum plasma concentration of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
3.4
(3.0 to 3.7)
rVWF [N=14]
3.2
(2.8 to 3.7)
35.Secondary Outcome
Title PK50 - Elimination Phase Half-Life of VWF:CB
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant FVIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
rVWF:rFVIII [N=16]
19.3
(14.9 to 23.4)
rVWF [N=14]
18.3
(17.4 to 24.8)
36.Secondary Outcome
Title PK50 - Volume of Distribution at Steady State of VWF:CB
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants[N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg
rVWF:rFVIII [N=16]
0.35
(0.31 to 0.40)
rVWF [N=14]
0.36
(0.28 to 0.42)
37.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
145.4
(118.8 to 189.5)
rVWF [N=14]
113.0
(93.0 to 167.4)
38.Secondary Outcome
Title PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII], or 50 IU/kg VWF:RCo rVWF administered together with saline (placebo) [rVWF] for participants in the PK50 arms (Arm 1 and Arm 2). Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours*U/dL)/(U VWF: RCo/kg)
rVWF:rFVIII [N=16]
127.8
(112.3 to 145.1)
rVWF [N=14]
101.8
(74.4 to 124.4)
39.Secondary Outcome
Title PK50 - Mean Residence Time of FVIII:C
Hide Description Mean Residence Time (MRT) of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] for participants in the PK50 arms (Arm 1 and Arm 2).
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
44.0
(38.0 to 75.0)
40.Secondary Outcome
Title PK50 - Clearance of FVIII:C
Hide Description Clearance (CL) of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] for participants in the PK50 arms (Arm 1 and Arm 2).
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
0.007
(0.006 to 0.009)
41.Secondary Outcome
Title PK50 - Incremental Recovery of FVIII:C
Hide Description Incremental Recovery (IR) at the maximum plasma concentration of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] for participants in the PK50 arms (Arm 1 and Arm 2).
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Overall Study Arm
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[Not Specified]
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
2.3
(1.9 to 2.7)
42.Secondary Outcome
Title PK50 - Elimination Phase Half-Life of FVIII:C
Hide Description Elimination Phase Half-Life (T1/2) of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant FVIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] for participants in the PK50 arms (Arm 1 and Arm 2).
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: hours
24.8
(20.1 to 50.5)
43.Secondary Outcome
Title PK50 - Volume of Distribution at Steady State of FVIII:C
Hide Description Volume of Distribution at Steady State (Vss) of Factor VIII activity (FVIII:C) after infusion of 50 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) (ratio of 1.3:1±0.2) [rVWF:rFVIII] for participants in the PK50 arms (Arm 1 and Arm 2).
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK50 Arms
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (50 IU/kg recombinant von Willebrand Factor (rVWF) administered together with 38.5 IU/kg recombinant Factor VIII (rFVIII) [rVWF:rFVIII] or 50 IU/kg rVWF administered together with saline [rVWF]) i.e. a total participants from Arm 1 [PK50+Treatment] and Arm 2 [PK50 only]. Participants in the PK50 arms have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included from the PK50 arms.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: dL/kg
0.32
(0.29 to 0.44)
44.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
36.9
(29.2 to 41.7)
PK2 of rVWF [N=13]
38.9
(28.1 to 43.3)
45.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
35.6
(28.9 to 41.2)
PK2 of rVWF [N=13]
37.9
(25.9 to 41.8)
46.Secondary Outcome
Title PK80 - Mean Residence Time of VWF:RCo
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
26.4
(20.9 to 31.1)
PK2 of rVWF [N=13]
26.4
(23.7 to 32.8)
47.Secondary Outcome
Title PK80 - Clearance of VWF:RCo
Hide Description Clearance (CL) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
PK1 of rVWF [N=15]
0.027
(0.024 to 0.034)
PK2 of rVWF [N=13]
0.026
(0.023 to 0.036)
48.Secondary Outcome
Title PK80 - Incremental Recovery of VWF:RCo
Hide Description Incremental Recovery (IR) at the maximum plasma concentration Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
1.8
(1.7 to 2.2)
PK2 of rVWF [N=13]
1.8
(1.6 to 2.0)
49.Secondary Outcome
Title PK80 - Elimination Phase Half-Life of VWF:Co
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
18.4
(16.4 to 22.1)
PK2 of rVWF [N=13]
19.8
(15.2 to 23.6)
50.Secondary Outcome
Title PK80 - Volume of Distribution at Steady State of VWF:RCo
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Ristocetin cofactor (VWF:RCo) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study. PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg
PK1 of rVWF [N=15]
0.78
(0.58 to 0.86)
PK2 of rVWF [N=13]
0.75
(0.58 to 1.01)
51.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
66.6
(50.4 to 89.4)
PK2 of rVWF [N=13]
86.9
(54.9 to 100.5)
52.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
61.3
(48.8 to 73.7)
PK2 of rVWF [N=13]
77.4
(53.0 to 87.6)
53.Secondary Outcome
Title PK80 - Mean Residence Time of VWF:Ag
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
38.4
(31.9 to 48.1)
PK2 of rVWF [N=13]
36.9
(30.0 to 50.8)
54.Secondary Outcome
Title PK80 - Clearance of VWF:Ag
Hide Description Clearance (CL) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
PK1 of rVWF [N=15]
0.015
(0.011 to 0.020)
PK2 of rVWF [N=13]
0.012
(0.010 to 0.018)
55.Secondary Outcome
Title PK80 - Incremental Recovery of VWF:Ag
Hide Description Incremental Recovery (IR) at the maximum plasma concentration Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
2.2
(1.9 to 2.6)
PK2 of rVWF [N=13]
2.4
(2.0 to 2.9)
56.Secondary Outcome
Title PK80 - Elimination Phase Half-Life of VWF:Ag
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
27.5
(22.5 to 34.0)
PK2 of rVWF [N=13]
24.8
(21.1 to 37.7)
57.Secondary Outcome
Title PK80 - Volume of Distribution at Steady State of VWF:Ag
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Antigen (VWF:Ag) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg
PK1 of rVWF [N=15]
0.55
(0.46 to 0.61)
PK2 of rVWF [N=13]
0.50
(0.41 to 0.57)
58.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
73.9
(57.3 to 96.2)
PK2 of rVWF [N=13]
90.8
(66.0 to 105.2)
59.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participatns from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
71.9
(57.0 to 89.8)
PK2 of rVWF [N=13]
88.1
(63.8 to 96.3)
60.Secondary Outcome
Title PK80 - Mean Residence Time of VWF:CB
Hide Description Mean Residence Time (MRT) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
30.9
(24.3 to 35.0)
PK2 of rVWF [N=13]
28.7
(25.6 to 37.2)
61.Secondary Outcome
Title PK80 - Clearance of VWF:CB
Hide Description Clearance (CL) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg/hours
PK1 of rVWF [N=15]
0.014
(0.010 to 0.017)
PK2 of rVWF [N=13]
0.011
(0.010 to 0.015)
62.Secondary Outcome
Title PK80 - Incremental Recovery of VWF:CB
Hide Description Incremental Recovery (IR) at the maximum plasma concentration Area under the plasma concentration curve (AUC) from time 0 to infinity of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
3.1
(2.8 to 3.6)
PK2 of rVWF [N=13]
3.7
(2.7 to 4.0)
63.Secondary Outcome
Title PK80 - Elimination Phase Half-Life of VWF:CB
Hide Description Elimination Phase Half-Life (T1/2) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
PK1 of rVWF [N=15]
18.8
(16.6 to 24.9)
PK2 of rVWF [N=13]
20.9
(17.8 to 23.5)
64.Secondary Outcome
Title PK80 - Volume of Distribution at Steady State of VWF:CB
Hide Description Volume of Distribution at Steady State (Vss) of von Willebrand Factor Collagen Binding (VWF:CB) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: dL/kg
PK1 of rVWF [N=15]
0.39
(0.34 to 0.46)
PK2 of rVWF [N=13]
0.36
(0.33 to 0.40)
65.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity of Factor VIII activity (FVIII:C) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
96.8
(64.0 to 126.5)
PK2 of rVWF [N=13]
94.8
(60.4 to 106.5)
66.Secondary Outcome
Title PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
Hide Description Area under the plasma concentration curve (AUC) from time 0 to 96 hours of Factor VIII activity (FVIII:C) after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. Category title includes number of participants [N] who provided data for the category.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: (hours*U/dL)/(U VWF: RCo/kg)
PK1 of rVWF [N=15]
81.7
(54.7 to 104.3)
PK2 of rVWF [N=13]
71.8
(49.6 to 89.2)
67.Secondary Outcome
Title PK80- Ratio of Intra-participant PK of VWF:RCo, VWF:Ag and VWF:CB at Baseline and After 6 Months
Hide Description Area under the plasma concentration curve (AUC) from time 0 to infinity per dose (AUC0-∞/dose) for von Willebrand Factor Ristocetin cofactor (VWF:RCo), von Willebrand Factor Antigen (VWF:Ag) and von Willebrand Factor Collagen Binding (VWF:CB). Each parameter was compared between the two PK assessments after infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] for participants in the PK80 arm (participants from Arm 3 with PK80 data only). PK assessment conducted at first infusion of 80 IU/kg rWVF [PK1] and the second infusion of 80 IU/kg rVWF after participants were treated on demand for bleeding episodes for at least 6 months since their first infusion of study product [PK2]. 13 participants had data available for this endpoint i.e. data for PK1 and PK2.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the PK80 Arm who had pharmacokinetic (PK) data available after both the first infusion of 80 IU/kg recombinant von Willebrand Factor:von Willebrand Factor Ristocetin cofactor (VWF:RCo rVWF) [rVWF] [PK1] and the second infusion of 80 IU/kg rVWF [PK2].
Arm/Group Title PK80 Arm
Hide Arm/Group Description:
Comprised of participants who underwent PK analysis of study product (80 IU/kg recombinant von Willebrand Factor [rVWF]) i.e. participants from Arm 3 [PK80+Treatment]. Participants in this arm have received at least one PK infusion and have provided data suitable for PK analysis. Only PK data included in this arm.
Overall Number of Participants Analyzed 13
Geometric Mean (90% Confidence Interval)
Unit of Measure: ratio of AUC0-∞/dose
AUC0-∞/dose - VWF:RCo
0.9587
(0.8466 to 1.0857)
AUC0-∞/dose - VWF:Ag
1.0914
(1.0132 to 1.1757)
AUC0-∞/dose - VWF:CB
1.0666
(1.0004 to 1.1372)
Time Frame For 12 months after first infusion of recombinant von Willebrand Factor (rVWF) with or without recombinant Factor VIII (rVWF:rFVIII)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description Comprises of participants who were treated with study product (recombinant von Willebrand Factor [rVWF] with or without recombinant factor VIII [rFVIII]) at least once during the study.
All-Cause Mortality
Safety Analysis Set
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Safety Analysis Set
Affected / at Risk (%) # Events
Total   7/37 (18.92%)    
Gastrointestinal disorders   
Constipation  1  1/37 (2.70%)  1
Gastrointestinal haemorrhage  1  1/37 (2.70%)  1
Haemorrhoids  1  1/37 (2.70%)  1
Mesenteric haematoma  1  1/37 (2.70%)  1
General disorders   
Chest discomfort  1  1/37 (2.70%)  1
Infections and infestations   
Osteomyelitis  1  1/37 (2.70%)  1
Heart rate increased  1  1/37 (2.70%)  1
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/37 (2.70%)  1
Reproductive system and breast disorders   
Uterine polyp  1  1/37 (2.70%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Safety Analysis Set
Affected / at Risk (%) # Events
Total   14/37 (37.84%)    
Blood and lymphatic system disorders   
Anaemia  1  2/37 (5.41%)  2
Iron deficiency anaemia  1  3/37 (8.11%)  4
Ear and labyrinth disorders   
Vertigo  1  2/37 (5.41%)  3
Gastrointestinal disorders   
Nausea  1  2/37 (5.41%)  2
Vomiting  1  3/37 (8.11%)  4
General disorders   
Infusion site paraesthesia  1  2/37 (5.41%)  2
Infections and infestations   
Upper respiratory tract infection  1  3/37 (8.11%)  5
Injury, poisoning and procedural complications   
Contusion  1  2/37 (5.41%)  2
Laceration  1  2/37 (5.41%)  4
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/37 (8.11%)  16
Back pain  1  2/37 (5.41%)  3
Nervous system disorders   
Headache  1  4/37 (10.81%)  12
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Baxter's 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 the earlier of the primary multicenter publication or ≥12 months after study completion. Baxter requires a review of results communications (e.g., for confidential information) ≥40 days prior to submission or communication. Baxter may request an additional delay of ≤45 days eg, for intellectual property protection.
Results Point of Contact
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
Responsible Party: Shire ( Baxalta now part of Shire )
ClinicalTrials.gov Identifier: NCT01410227     History of Changes
Other Study ID Numbers: 071001
2010-024108-84 ( EudraCT Number )
First Submitted: August 4, 2011
First Posted: August 5, 2011
Results First Submitted: March 21, 2016
Results First Posted: April 21, 2016
Last Update Posted: May 21, 2019