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rVWF IN PROPHYLAXIS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02973087
Recruitment Status : Active, not recruiting
First Posted : November 25, 2016
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

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).

Condition or disease Intervention/treatment Phase
Von Willebrand Disease Biological: von Willebrand factor (Recombinant) Biological: Antihemophilic Factor (Recombinant) Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A PROSPECTIVE, PHASE 3, OPEN-LABEL, INTERNATIONAL MULTICENTER STUDY ON EFFICACY AND SAFETY OF PROPHYLAXIS WITH rVWF IN SEVERE VON WILLEBRAND DISEASE
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : August 17, 2020
Estimated Study Completion Date : August 17, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All Study Participants
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).
Biological: von Willebrand factor (Recombinant)
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.
Other Names:
  • BAX 111
  • rVWF
  • VONVENDI
  • vonicog alfa
  • BAX111

Biological: Antihemophilic Factor (Recombinant)
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.
Other Names:
  • ADVATE
  • Recombinant Factor VIII
  • rFVIII




Primary Outcome Measures :
  1. Annualized Bleeding Rate (ABR) [ Time Frame: Up to approximately 15 months ]
    ABR will be assessed for spontaneous (not related to trauma) bleeding episodes during prophylactic treatment with rVWF (vonicog alfa).


Secondary Outcome Measures :
  1. Annualized Bleeding Rate (ABR) Percent Reduction Success for On-Demand (OD) Participants [ Time Frame: Up to approximately 15 months ]
    ABR percent reduction success for OD participants is defined as at least 25% reduction of ABR for spontaneous (not related to trauma) bleeding episodes during recombinant von Willebrand factor (rVWF) (vonicog alfa) prophylaxis relative to the participant's own historical ABR during on-demand treatment.

  2. Annualized Bleeding Rate (ABR) Preservation Success for Plasma Derived Von Willebrand Factor Product (pdVWF) Switch Participants [ Time Frame: Up to approximately 15 months ]
    ABR preservation success for pdVWF switch participants is defined as achieving an ABR for spontaneous bleeding episodes during rVWF (vonicog alfa) prophylaxis that is no greater than the participant's own historical ABR during prophylactic treatment with plasma derived von Willebrand factor (pdVWF).

  3. Categorized Spontaneous Annualized Bleeding Rate (ABR) [ Time Frame: Up to approximately 15 months ]
    Categorized spontaneous ABR is defined as 0, 1-2, 3-5, or greater than (>) 5 bleeding episodes during the prophylactic treatment with rVWF (vonicog alfa). Bleeding occurring at multiple locations related to the same injury will be counted as a single bleeding episode.

  4. Total Number of Infusions and the Average Number of Infusions per Week [ Time Frame: Up to approximately 15 months ]
    Total number of infusions and the average number of infusions per week during prophylactic treatment with rVWF (vonicog alfa) will be assessed.

  5. Total Weight Adjusted Consumption of Recombinant Von Willebrand Factor (rVWF) [ Time Frame: Up to approximately 15 months ]
    Total weight adjusted consumption of rVWF (vonicog alfa) during prophylactic treatment will be assessed.

  6. Spontaneous Annualized Bleeding Rate (ABR) by Location of Bleeding [ Time Frame: Up to approximately 15 months ]
    Spontaneous ABR by location of bleeding (GI, epistaxis, joint bleeding, menorrhagia, oral and other mucosa, muscle and soft tissue, etc.) while on prophylactic treatment with rVWF (vonicog alfa).

  7. Incidence, Severity, Causality of Adverse Events (AEs) [ Time Frame: Up to approximately 15 months ]
    An AE is defined as any untoward medical occurrence in a participant administered Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom (e.g., rash, pain, discomfort, fever, dizziness, etc.), disease (e.g., peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Incidence, severity, causality of adverse events will be assessed.

  8. Adverse Events Related to Thromboembolic Events [ Time Frame: Up to approximately 15 months ]
    Adverse events of special interest (AESI) such as thromboembolic events will be assessed throughout the study.

  9. Adverse Events Related to Hypersensitivity Reactions [ Time Frame: Up to approximately 15 months ]
    Adverse events of special interest (AESI) such as hypersensitivity reactions will be assessed.

  10. Number of Participants with Development of Neutralizing Antibodies to von Willebrand Factor (rVWF) and Factor VIII (FVIII) [ Time Frame: Up to approximately 15 months ]
    Number of participants who develop neutralizing antibodies to VWF and FVIII will be assessed.

  11. Number of Participants with Development of Total Binding Antibodies to von Willebrand factor (rVWF) and Factor VIII (FVIII) [ Time Frame: Up to approximately 15 months ]
    Number of participants who develop total binding antibodies to VWF and FVIII will be assessed.

  12. Number of Participants with Development of Binding Antibodies to CHO proteins, mouse immunoglobulin G (IgG) and rFurin [ Time Frame: Up to approximately 15 months ]
    Number of participants who develop antibodies to Chinese hamster ovary (CHO) proteins, mouse immunoglobulin G (IgG) and recombinant Furin (rFurin) will be assessed.

  13. Number of Participants With Clinically Significant Changes in Vital Signs From Baseline [ Time Frame: Up to approximately 15 months ]
    Vital signs will include blood pressure, pulse rate, respiratory rate and body temperature. Number of participants with clinically significant changes in vital signs from baseline will be assessed.

  14. Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters From Baseline [ Time Frame: Up to approximately 15 months ]
    Clinical laboratory parameters will include hematology and clinical chemistry assessments. Number of participants with clinically significant changes in clinical laboratory parameters from baseline will be assessed.

  15. Pharmacokinetics (PK) - Incremental recovery (IR) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  16. Pharmacokinetics - Incremental recovery (IR) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  17. Pharmacokinetics - Incremental recovery (IR) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  18. Pharmacokinetics - Terminal half-life (T1/2) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  19. Pharmacokinetics - Terminal half-life (T1/2) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  20. Pharmacokinetics - Terminal half-life (T1/2) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  21. Pharmacokinetics - Mean residence time (MRT) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  22. Pharmacokinetics - Mean residence time (MRT) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  23. Pharmacokinetics - Mean residence time (MRT) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  24. Pharmacokinetics - Area under the concentration versus time curve from 0 to infinity (AUC0-∞) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  25. Pharmacokinetics - Area under the concentration versus time curve from 0 to infinity (AUC0-∞) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  26. Pharmacokinetics - Area under the concentration versus time curve from 0 to infinity (AUC0-∞) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  27. Pharmacokinetics - Area under the concentration versus time curve from 0 to the last measurable concentration (AUC0-tlast) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  28. Pharmacokinetics - Area under the concentration versus time curve from 0 to the last measurable concentration (AUC0-tlast) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  29. Pharmacokinetics - Area under the concentration versus time curve from 0 to the last measurable concentration (AUC0-tlast) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  30. Pharmacokinetics - Maximum plasma concentration (Cmax) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  31. Pharmacokinetics - Maximum plasma concentration (Cmax) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  32. Pharmacokinetics - Maximum plasma concentration (Cmax) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  33. Pharmacokinetics - minimum time to reach the maximum concentration (Tmax) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  34. Pharmacokinetics - minimum time to reach the maximum concentration (Tmax) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  35. Pharmacokinetics - minimum time to reach the maximum concentration (Tmax) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  36. Pharmacokinetics - Volume of distribution at steady state (Vss) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  37. Pharmacokinetics - Volume of distribution at steady state (Vss) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  38. Pharmacokinetics - Volume of distribution at steady state (Vss) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  39. Pharmacokinetics - Clearance (CL) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]

    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

    Pharmacokinetic (PK) parameters, based on the initial PK assessment after a washout for on-demand participants


  40. Pharmacokinetics - Clearance (CL) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  41. Pharmacokinetics - Clearance (CL) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PK parameters, based on the initial PK assessment after a washout for on-demand participants will be assessed.

  42. Pharmacodynamics (PD): Maximum plasma concentration (Cmax) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters after a washout for on-demand participants measured in Factor VIII (FVIII) activity by the 1-stage clotting assay (FVIII:C) will be assessed.

  43. Pharmacodynamics (PD): minimum time to reach the maximum concentration (Tmax) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters after a washout for on-demand participants measured in Factor VIII (FVIII) activity by the 1-stage clotting assay (FVIII:C) will be assessed.

  44. Pharmacodynamics (PD): Area under the concentration versus time curve from 0 to the last measurable concentration (AUC0-tlast) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters after a washout for on-demand participants measured in Factor VIII (FVIII) activity by the 1-stage clotting assay (FVIII:C) will be assessed.

  45. Pharmacokinetics at Steady State - Area under the concentration versus time curve from 0 to end of the partial dosing interval (AUC0- tau;ss) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  46. Pharmacokinetics at Steady State - Area under the concentration versus time curve from 0 to end of the partial dosing interval (AUC0- tau;ss) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  47. Pharmacokinetics at Steady State - Area under the concentration versus time curve from 0 to end of the partial dosing interval (AUC0- tau;ss) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  48. Pharmacokinetics at Steady State - maximum concentration during the partial dosing interval (Cmax;ss) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  49. Pharmacokinetics at Steady State - maximum concentration during the partial dosing interval (Cmax;ss) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  50. Pharmacokinetics at Steady State - maximum concentration during the partial dosing interval (Cmax;ss) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  51. Pharmacokinetics at Steady State - minimum time to reach the maximum concentration (Tmax;ss) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  52. Pharmacokinetics at Steady State - minimum time to reach the maximum concentration (Tmax;ss) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  53. Pharmacokinetics at Steady State - minimum time to reach the maximum concentration (Tmax;ss) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  54. Pharmacokinetics at Steady State - minimum concentration during the partial dosing interval (Cmin;ss) based on Von Willebrand factor: Ristocetin cofactor (VWF:Rco) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  55. Pharmacokinetics at Steady State - minimum concentration during the partial dosing interval (Cmin;ss) based on Von Willebrand factor antigen (VWF:Ag) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  56. Pharmacokinetics at Steady State - minimum concentration during the partial dosing interval (Cmin;ss) based on Von Willebrand Factor collagen binding (VWF:CB) activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    For on-demand and switch participants.

  57. Pharmacodynamics (PD) at Steady State: Area under the plasma concentration /time curve from time 0 to end of the partial dosing interval (AUC0-tau;ss) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters at steady state will be assessed shortly for both on demand (OD) and switch cohorts after reaching steady state as measured in FVIII activity by the 1-stage clotting assay.

  58. Pharmacodynamics (PD) at Steady State: Maximum plasma concentration during the partial dosing interval at steady state (Cmax;ss) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters at steady state will be assessed shortly for both on demand and switch cohorts after reaching steady state as measured in FVIII activity by the 1-stage clotting assay.

  59. Pharmacodynamics (PD) at Steady State: Minimum time to reach the maximum concentration at steady state (Tmax;ss) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters at steady state will be assessed shortly for both on demand and switch cohorts after reaching steady state as measured in FVIII activity by the 1-stage clotting assay.

  60. Pharmacodynamics (PD) at Steady State: Minimum plasma concentration during the partial dosing interval at steady state (Cmin;ss) [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    PD parameters at steady state will be assessed shortly for both on demand and switch cohorts after reaching steady state as measured in FVIII activity by the 1-stage clotting assay.

  61. Factor VIII (FVIII) clotting activity [ Time Frame: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours ]
    Time course of FVIII clotting activity (FVIII:C) levels will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02973087


Locations
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Sponsors and Collaborators
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Investigators
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Study Director: Study Director Shire
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Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02973087    
Other Study ID Numbers: 071301
2016-001478-14 ( EudraCT Number )
First Posted: November 25, 2016    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. 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.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants