Clinical trial NCT01410227: Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)
Official title: A Phase 3 Clinical Study to Determine the Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor : Recombinant Factor VIII (rVWF:rFVIII) and rVWF in the Treatment of Bleeding Episodes in Subjects Diagnosed With Von Willebrand Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Von Willebrand Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-08-05
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this Phase 3 study is to assess the pharmacokinetics of rVWF:rFVIII and rVWF, and to assess the safety and efficacy of rVWF:rFVIII and rVWF in the treatment of bleeding events in subjects with severe hereditary von Willebrand disease (VWD).


Eligibility criteria: Inclusion Criteria:

* Participant has been diagnosed with:

  1. Type 1 (Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) \< 20 IU/dL) or,
  2. Type 2A (VWF:RCo \< 20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII activity (FVIII:C) \<10% and historically documented genetics), Type 2M or,
  3. Type 3 ( Von Willebrand factor antigen (VWF:Ag) ≤ 3 IU/dL) or,
  4. Severe Von Willebrand disease (VWD) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding
* Participant, who participates in the treatment for bleeding episodes, has had a minimum of 1 documented bleed (medical history) requiring VWF coagulation factor replacement therapy during the previous 12 months prior to enrollment.
* Participant has a Karnofsky score ≥ 60%
* Participant is at least 18 and not older than 65 years of age at enrollment
* If female of childbearing potential, participant presents with a negative pregnancy test
* Participant agrees to employ adequate birth control measures for the duration of the study
* Participant is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

* Participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or elevated PT/international normalized ratio \[INR\] \>1.4).
* Participant has a documented history of a VWF:RCo half-life of \<6 hours.
* Participant has a history or presence of a VWF inhibitor at screening.
* Participant has a history or presence of a factor VIII (FVIII) inhibitor with a titer ≥0.4 BU (by Nijmegen assay) or ≥ 0.6 BU (by Bethesda assay).
* Participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
* Participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
* Participant has a medical history of a thromboembolic event.
* Participant is HIV positive with an absolute CD4 count \<200/mm3.
* Participant has been diagnosed with cardiovascular disease (New York Heart Association \[NYHA\] classes 1-4.
* Participant has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, non-seasonal asthma) at screening.
* Participant has been diagnosed with significant liver disease as evidenced by any of the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices).
* Participant has been diagnosed with renal disease, with a serum creatinine level ≥2 mg/dL.
* In the judgment of the investigator, the participant has another clinically significant concomitant disease (eg, uncontrolled hypertension) that may pose additional risks for the participant.
* Participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment
* Participant is pregnant or lactating at the time of enrollment.
* Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study.
* Participant has a history of drug or alcohol abuse within the 2 years prior to enrollment.
* Participant has a progressive fatal disease and/or life expectancy of less than 3 months.
* Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
* Participant suffers from a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
* Participant is in prison or compulsory detention by regulatory and/or juridical order

Primary outcomes:
measure: Percentage of Participants With Treatment Success for Treated Bleeding Episodes
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
Secondary outcomes:
measure: Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good"
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good", Excluding Gastrointestinal Bleeds
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Number of Infusions of rVWF:rFVIII and/or rVWF Per Bleeding Episode
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Number of Units of rVWF:rFVIII and/or rVWF Per Bleeding Episode
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Inhibitory Antibodies to FVIII
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Inhibitory Antibodies to VWF
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Binding Antibodies to VWF
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Binding Antibodies to CHO
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Binding Antibodies to rFurin
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Develop Binding Antibodies to Mouse Immunoglobulin
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Percentage of Participants Who Had an Occurrence of Thrombotic Events
timeFrame: After signing informed consent until 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Number of Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Number of Participants With Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: Number of Adverse Events by Infusion Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs
timeFrame: For 12 months after first infusion of rVWF:rFVIII or rVWF
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Mean Residence Time of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Clearance of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Incremental Recovery of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Elimination Phase Half-Life of VWF:Co
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Volume of Distribution at Steady State of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout
measure: PK50 - Mean Residence Time of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Clearance of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Incremental Recovery of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Elimination Phase Half-Life of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Volume of Distribution at Steady State of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Mean Residence Time of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Clearance of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Incremental Recovery of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Elimination Phase Half-Life of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Volume of Distribution at Steady State of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Mean Residence Time of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Clearance of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Incremental Recovery of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Elimination Phase Half-Life of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK50 - Volume of Distribution at Steady State of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Mean Residence Time of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Clearance of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Incremental Recovery of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Elimination Phase Half-Life of VWF:Co
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Volume of Distribution at Steady State of VWF:RCo
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Mean Residence Time of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Clearance of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Incremental Recovery of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Elimination Phase Half-Life of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Volume of Distribution at Steady State of VWF:Ag
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Mean Residence Time of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Clearance of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Incremental Recovery of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Elimination Phase Half-Life of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Volume of Distribution at Steady State of VWF:CB
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
measure: PK80- Ratio of Intra-participant PK of VWF:RCo, VWF:Ag and VWF:CB at Baseline and After 6 Months
timeFrame: PK evaluations at pre-infusion, then at 15, 30 and 60 mins, and 3, 6, 12, 24, 30, 48, 72 and 96 hrs post-infusion. PK evaluation timeframe for 28 ± 3 days after first infusion of study product which includes PK evaluation for both infusions and washout.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Peoria
country: United States
facility: University of Illinois College of Medicine at Peoria
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Rochester
country: United States
facility: The Mary M Gooley Hemophilia Center and Rochester General Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Milwaukee
country: United States
facility: Blood Center of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Vienna
country: Austria
facility: Medical University Vienna
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Sofia
country: Bulgaria
facility: Specialized Haematological Hospital "Joan Pavel"
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina"
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Duisburg
country: Germany
facility: Gerinnungszentrum Rhein-Ruhr
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz
city: Pune
country: India
facility: Jehangir Clinical Development Centre Pvt. Ltd.
city: Pune
country: India
facility: Sahyadri Speciality Hospital
city: Vellore
country: India
facility: Christian Medical College
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Università degli Studi di Roma "La Sapienza"
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Ogikubo Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Gdansk
country: Poland
facility: Hematology and Transplantology Clinic, University Clinic Centre - Medical University Hospital
city: Krakow
country: Poland
facility: Nicolaus Copernicus Provincial Specialist Hospital in Lodz Department of Hematology
city: Warsaw
country: Poland
facility: Institute of Haematology and Transfusion Medicine
city: Wroclaw
country: Poland
facility: Independent Public Clinical Hospital No. 1 in Wroclaw, Department of Hematology, blood cancer and Bone Marrow Transplantation
city: Ekaterinburg
country: Russian Federation
facility: Regional Pediatric Clinical Hospital #1
city: Kirov
country: Russian Federation
facility: Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia
city: Krasnoyarsk
country: Russian Federation
facility: Territorial Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Municipal Policlinic # 37
city: a Coruña
country: Spain
facility: Hospital Materno Infantil Teresa Herrera
state: Galicia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario La Paz
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Malmö
country: Sweden
facility: Skåne University Hospital (SUS)
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Gill JC, Castaman G, Windyga J, Kouides P, Ragni M, Leebeek FW, Obermann-Slupetzky O, Chapman M, Fritsch S, Pavlova BG, Presch I, Ewenstein B. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015 Oct 22;126(17):2038-46. doi: 10.1182/blood-2015-02-629873. Epub 2015 Aug 3.