Clinical trial NCT02973087: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Von Willebrand Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2016-11-25
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Up to 12 months
Secondary outcomes:
measure: Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12
timeFrame: Up to 12 months
measure: Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12
timeFrame: Up to 12 months
measure: Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12
timeFrame: Baseline through Month 12
measure: Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12
timeFrame: Up to 12 months
measure: Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12
timeFrame: Up to 12 months
measure: Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12
timeFrame: Up to 12 months
measure: Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12
timeFrame: Up to 12 months
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose of study drug up to end of study (approximately 32 months)
measure: Number of Participants Based on Severity of TEAEs
timeFrame: From first dose of study drug up to end of study (approximately 32 months)
measure: Number of Participants With TEAEs Based Causality
timeFrame: From first dose of study drug up to end of study (approximately 32 months)
measure: Number of Participants With Thromboembolic Events
timeFrame: From first dose of study drug up to end of study (approximately 32 months)
measure: Number of Participants With Hypersensitivity Reactions
timeFrame: From first dose of study drug up to end of study (approximately 32 months)
measure: Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
timeFrame: Baseline through Month 12
measure: Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
timeFrame: Baseline through Month 12
measure: Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin
timeFrame: Baseline through Month 12
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to end of study (approximately 32 months)
measure: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
timeFrame: Baseline up to end of study (approximately 32 months)
measure: Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
timeFrame: 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
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
timeFrame: 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
measure: Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity
timeFrame: 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
measure: Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Factor VIII (FVIII) Clotting Activity
timeFrame: 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
Other outcomes:
Locations:
city: Loveland
country: United States
facility: University of Colorado Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Aurora
country: United States
facility: University of Colorado Health
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest Unversity
state: North Carolina
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
city: Brest
country: France
facility: Hôpital Morvan
state: Finistere
city: Bron cedex
country: France
facility: Groupement Hospitalier Est- Hôpital Louis Pradel
city: Caen cedex 9
country: France
facility: CHU CAEN - Hôpital de la Côte de Nacre
city: Dijon cedex
country: France
facility: CHU Dijon - Hopital du Bocage
city: Lille Cedex
country: France
facility: Hopital Cardiologique - CHU Lille
city: Duisburg
country: Germany
facility: Coagulation Research Centre GmbH
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Hannover
country: Germany
facility: Werlhof-Institut GmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Barnaul
country: Russian Federation
facility: SBEI HPE Altai State Medical University of MoH and SD
city: Kemerovo
country: Russian Federation
facility: SAIH "Kemerovo Regional Clinical Hospital"
city: Kirov
country: Russian Federation
facility: FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
city: Kirov
country: Russian Federation
facility: FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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.