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rVWF IN PROPHYLAXIS

Primary Purpose

Von Willebrand Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
von Willebrand factor (Recombinant)
Antihemophilic Factor (Recombinant)
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Von Willebrand Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (<) 20 International Units/Deciliter [IU/dL]) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding

    1. Type 1 (VWF:RCo <20 IU/dL) or,
    2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,
    3. Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to [< or =] 3 IU/dL).
  2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening.
  3. For on-demand patient group, participant currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator.
  4. For Plasma derived von Willebrand factor (pdVWF) product switch patient group, participant has been receiving prophylactic treatment of pdVWF products for no less than 12 months prior to screening.
  5. For on-demand patient group, participant has greater than or equal to (>or=) 3 documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand factor (VWF) treatment during the past 12 months.
  6. Availability of records to reliably evaluate type, frequency and treatment of bleeding episodes during at least 12 months preceding enrollment. Up to 24 months retrospective data should be collected if available. Availability of dosing and factor consumption during 12 months (up to 24 months) of treatment prior to enrollment is required for pdVWF switch participants and is desired (but not a requirement) for on-demand participants.
  7. Participant is > or = 18 years old at the time of screening and has a body mass index > or = 15 but <40 kilogram per meter square (kg/m^2).
  8. If female of childbearing potential, participant presents with a negative blood/urine pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study.
  9. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  1. The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or prothrombin time [PT]/international normalized ratio [INR] greater than [>]1.4).
  2. The participant is currently receiving prophylactic treatment with more than 5 infusions per week.
  3. The participant is currently receiving prophylactic treatment with a weekly dose exceeding 240 IU/kg.
  4. The participant has a history or presence of a VWF inhibitor at screening.
  5. The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer ≥0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or > or = 0.6 Bethesda Unit (BU) (by Bethesda assay).
  6. The participant has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.
  7. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
  8. The participant has a medical history of a thromboembolic event.
  9. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count <200/ cubic millimeter (mm^3).
  10. The participant has been diagnosed with significant liver disease per investigator's medical assessment of the participant's current condition or medical history or as evidenced by any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices).
  11. The participant has been diagnosed with renal disease, with a serum creatinine (CR) level > or = 2.5 milligram per deciliter (mg/dL).
  12. The participant has a platelet count <100,000/ milliliter (mL) at screening.
  13. The participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to signing the informed consent.
  14. The participant is pregnant or lactating at the time of enrollment.
  15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
  16. The participant has participated in another clinical study involving another Investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
  17. The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
  18. The participant is scheduled for a surgical intervention.
  19. The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
  20. The participant has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
  21. The participant is in prison or compulsory detention by regulatory and/or juridical order.
  22. The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.

Sites / Locations

  • University of Colorado Health
  • University of Florida College of Medicine
  • University of Florida College of Medicine
  • Bleeding and Clotting Disorders Institute
  • University of Colorado Health
  • Indiana Hemophilia and Thrombosis Center
  • Henry Ford Hospital
  • Comprehensive Cancer Center of Wake Forest Unversity
  • Hamilton Health Sciences Centre
  • Hôpital Morvan
  • Groupement Hospitalier Est- Hôpital Louis Pradel
  • CHU CAEN - Hôpital de la Côte de Nacre
  • CHU Dijon - Hopital du Bocage
  • Hopital Cardiologique - CHU Lille
  • Coagulation Research Centre GmbH
  • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Werlhof-Institut GmbH
  • Medizinische Hochschule Hannover
  • Azienda Ospedaliera Universitaria Careggi
  • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Ospedale Pediatrico Bambino Gesù
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Erasmus Medisch Centrum
  • SBEI HPE Altai State Medical University of MoH and SD
  • SAIH "Kemerovo Regional Clinical Hospital"
  • FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
  • FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
  • Hospital General Universitario de Alicante
  • Hospital Universitario La Paz
  • Hospital Universitari i Politecnic La Fe
  • Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
  • Ege University Medical Faculty
  • Ege University Medical Faculty
  • Ondokuz Mayis Univ. Med. Fac.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Study Participants

Arm Description

Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).

Outcomes

Primary Outcome Measures

Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12
ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).

Secondary Outcome Measures

Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12
For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.
Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12
For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.
Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12
The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (>) 0 through 2,>2 through 5,>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.
Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12
For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.
Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12
Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.
Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12
For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.
Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12
Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.
Number of Participants Based on Severity of TEAEs
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.
Number of Participants With TEAEs Based Causality
An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.
Number of Participants With Thromboembolic Events
Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.
Number of Participants With Hypersensitivity Reactions
Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.
Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
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). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin
Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.
Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
IR based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmax based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmax based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Tmax based on VWF:Rco activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Tmax based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Tmax based on VWF:CB activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.
Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity
Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity
Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity
AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity
AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.
Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Factor VIII (FVIII) Clotting Activity
FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.

Full Information

First Posted
November 22, 2016
Last Updated
August 5, 2021
Sponsor
Takeda
Collaborators
Baxalta Innovations GmbH, now part of Shire
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1. Study Identification

Unique Protocol Identification Number
NCT02973087
Brief Title
rVWF IN PROPHYLAXIS
Official Title
A PROSPECTIVE, PHASE 3, OPEN-LABEL, INTERNATIONAL MULTICENTER STUDY ON EFFICACY AND SAFETY OF PROPHYLAXIS WITH rVWF IN SEVERE VON WILLEBRAND DISEASE
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
November 16, 2017 (Actual)
Primary Completion Date
July 6, 2020 (Actual)
Study Completion Date
July 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Baxalta Innovations GmbH, now part of Shire

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this phase 3 study is to investigate the efficacy and safety, including immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with severe von Willebrand disease (VWD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Von Willebrand Disease

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All Study Participants
Arm Type
Experimental
Arm Description
Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).
Intervention Type
Biological
Intervention Name(s)
von Willebrand factor (Recombinant)
Other Intervention Name(s)
BAX 111, rVWF, VONVENDI, vonicog alfa, BAX111
Intervention Description
OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.
Intervention Type
Biological
Intervention Name(s)
Antihemophilic Factor (Recombinant)
Other Intervention Name(s)
ADVATE, Recombinant Factor VIII, rFVIII
Intervention Description
During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.
Primary Outcome Measure Information:
Title
Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12
Description
ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12
Description
For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.
Time Frame
Up to 12 months
Title
Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12
Description
For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.
Time Frame
Up to 12 months
Title
Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12
Description
The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (>) 0 through 2,>2 through 5,>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.
Time Frame
Baseline through Month 12
Title
Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12
Description
For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.
Time Frame
Up to 12 months
Title
Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12
Description
Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.
Time Frame
Up to 12 months
Title
Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12
Description
For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.
Time Frame
Up to 12 months
Title
Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12
Description
Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.
Time Frame
Up to 12 months
Title
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.
Time Frame
From first dose of study drug up to end of study (approximately 32 months)
Title
Number of Participants Based on Severity of TEAEs
Description
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.
Time Frame
From first dose of study drug up to end of study (approximately 32 months)
Title
Number of Participants With TEAEs Based Causality
Description
An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.
Time Frame
From first dose of study drug up to end of study (approximately 32 months)
Title
Number of Participants With Thromboembolic Events
Description
Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.
Time Frame
From first dose of study drug up to end of study (approximately 32 months)
Title
Number of Participants With Hypersensitivity Reactions
Description
Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
Time Frame
From first dose of study drug up to end of study (approximately 32 months)
Title
Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
Description
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.
Time Frame
Baseline through Month 12
Title
Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
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). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.
Time Frame
Baseline through Month 12
Title
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin
Description
Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.
Time Frame
Baseline through Month 12
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description
Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.
Time Frame
Baseline up to end of study (approximately 32 months)
Title
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
Description
Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.
Time Frame
Baseline up to end of study (approximately 32 months)
Title
Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
IR based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Cmax based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Cmax based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Tmax based on VWF:Rco activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Tmax based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Tmax based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity
Description
Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity
Description
Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity
Description
AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time Frame
At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Description
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Description
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Description
Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Description
AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Description
Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Description
Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Description
Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Title
Factor VIII (FVIII) Clotting Activity
Description
FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.
Time Frame
At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (<) 20 International Units/Deciliter [IU/dL]) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding Type 1 (VWF:RCo <20 IU/dL) or, Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or, Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to [< or =] 3 IU/dL). Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening. For on-demand patient group, participant currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator. For Plasma derived von Willebrand factor (pdVWF) product switch patient group, participant has been receiving prophylactic treatment of pdVWF products for no less than 12 months prior to screening. For on-demand patient group, participant has greater than or equal to (>or=) 3 documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand factor (VWF) treatment during the past 12 months. Availability of records to reliably evaluate type, frequency and treatment of bleeding episodes during at least 12 months preceding enrollment. Up to 24 months retrospective data should be collected if available. Availability of dosing and factor consumption during 12 months (up to 24 months) of treatment prior to enrollment is required for pdVWF switch participants and is desired (but not a requirement) for on-demand participants. Participant is > or = 18 years old at the time of screening and has a body mass index > or = 15 but <40 kilogram per meter square (kg/m^2). If female of childbearing potential, participant presents with a negative blood/urine pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study. Participant is willing and able to comply with the requirements of the protocol. Exclusion Criteria: The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or prothrombin time [PT]/international normalized ratio [INR] greater than [>]1.4). The participant is currently receiving prophylactic treatment with more than 5 infusions per week. The participant is currently receiving prophylactic treatment with a weekly dose exceeding 240 IU/kg. The participant has a history or presence of a VWF inhibitor at screening. The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer ≥0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or > or = 0.6 Bethesda Unit (BU) (by Bethesda assay). The participant has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies. The participant has a medical history of a thromboembolic event. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count <200/ cubic millimeter (mm^3). The participant has been diagnosed with significant liver disease per investigator's medical assessment of the participant's current condition or medical history or as evidenced by any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices). The participant has been diagnosed with renal disease, with a serum creatinine (CR) level > or = 2.5 milligram per deciliter (mg/dL). The participant has a platelet count <100,000/ milliliter (mL) at screening. The participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to signing the informed consent. The participant is pregnant or lactating at the time of enrollment. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia). The participant has participated in another clinical study involving another Investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. The participant has a progressive fatal disease and/or life expectancy of less than 15 months. The participant is scheduled for a surgical intervention. The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures. The participant has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude. The participant is in prison or compulsory detention by regulatory and/or juridical order. The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado Health
City
Loveland
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Florida College of Medicine
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Bleeding and Clotting Disorders Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
University of Colorado Health
City
Aurora
State/Province
Indiana
ZIP/Postal Code
80045
Country
United States
Facility Name
Indiana Hemophilia and Thrombosis Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Comprehensive Cancer Center of Wake Forest Unversity
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Hamilton Health Sciences Centre
City
Hamilton
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Hôpital Morvan
City
Brest
State/Province
Finistere
ZIP/Postal Code
29609
Country
France
Facility Name
Groupement Hospitalier Est- Hôpital Louis Pradel
City
Bron cedex
ZIP/Postal Code
69677
Country
France
Facility Name
CHU CAEN - Hôpital de la Côte de Nacre
City
Caen cedex 9
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Dijon - Hopital du Bocage
City
Dijon cedex
ZIP/Postal Code
21079
Country
France
Facility Name
Hopital Cardiologique - CHU Lille
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Coagulation Research Centre GmbH
City
Duisburg
ZIP/Postal Code
47051
Country
Germany
Facility Name
Klinikum der Johann Wolfgang Goethe-Universitaet
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Werlhof-Institut GmbH
City
Hannover
ZIP/Postal Code
30159
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Erasmus Medisch Centrum
City
Rotterdam
ZIP/Postal Code
3015 AA
Country
Netherlands
Facility Name
SBEI HPE Altai State Medical University of MoH and SD
City
Barnaul
ZIP/Postal Code
656038
Country
Russian Federation
Facility Name
SAIH "Kemerovo Regional Clinical Hospital"
City
Kemerovo
ZIP/Postal Code
650066
Country
Russian Federation
Facility Name
FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
City
Kirov
ZIP/Postal Code
610017
Country
Russian Federation
Facility Name
FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
City
Kirov
ZIP/Postal Code
610027
Country
Russian Federation
Facility Name
Hospital General Universitario de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Ege University Medical Faculty
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Ege University Medical Faculty
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Ondokuz Mayis Univ. Med. Fac.
City
Samsun
ZIP/Postal Code
55139
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
35439298
Citation
Leebeek FWG, Peyvandi F, Escobar M, Tiede A, Castaman G, Wang M, Wynn T, Baptista J, Wang Y, Zhang J, Mellgard B, Ozen G. Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results. Blood. 2022 Jul 14;140(2):89-98. doi: 10.1182/blood.2021014810.
Results Reference
derived
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b5fc34db2bf003ab45955
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

rVWF IN PROPHYLAXIS

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