Phase 3
N=37
Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)
Von Willebrand Disease
Bottom Line
View on ClinicalTrials.gov: NCT01410227 ↗Enrolled (actual)
37
Serious AEs
18.9%
Results posted
Apr 2016
Primary outcome: Primary: Percentage of Participants With Treatment Success for Treated Bleeding Episodes — 100.0 Percent of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Recombinant von Willebrand factor (rVWF) (Biological); Placebo (Drug); Recombinant factor VIIII (rFVIII) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Feb 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment Success for Treated Bleeding Episodes |
100.0 | — |
| SECONDARY Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good" |
100.0 | — |
| SECONDARY Percentage of Treated Bleeding Episodes With an Efficacy Rating of "Excellent" or "Good", Excluding Gastrointestinal Bleeds |
100.0 | — |
| SECONDARY Number of Infusions of rVWF:rFVIII and/or rVWF Per Bleeding Episode |
1.0 | — |
| SECONDARY Number of Units of rVWF:rFVIII and/or rVWF Per Bleeding Episode |
48.2 | — |
| SECONDARY Percentage of Participants Who Develop Inhibitory Antibodies to FVIII |
0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Develop Inhibitory Antibodies to VWF |
0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Develop Binding Antibodies to VWF |
0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Develop Binding Antibodies to CHO |
0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Develop Binding Antibodies to rFurin |
0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Develop Binding Antibodies to Mouse Immunoglobulin |
2.8; 0; 0 | — |
| SECONDARY Percentage of Participants Who Had an Occurrence of Thrombotic Events |
— | — |
| SECONDARY Number of Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY Number of Participants With Adverse Events Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY Number of Adverse Events by Infusion Related to Study Product Including Clinically Significant Changes in Laboratory Parameters and Vital Signs |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo |
32.4; 32.7 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo |
31.6; 31.3 | — |
| SECONDARY PK50 - Mean Residence Time of VWF:RCo |
25.2; 26.7 | — |
| SECONDARY PK50 - Clearance of VWF:RCo |
0.031; 0.031 | — |
| SECONDARY PK50 - Incremental Recovery of VWF:RCo |
1.8; 1.8 | — |
| SECONDARY PK50 - Elimination Phase Half-Life of VWF:Co |
16.6; 19.4 | — |
| SECONDARY PK50 - Volume of Distribution at Steady State of VWF:RCo |
0.70; 0.83 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag |
67.8; 67.1 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag |
62.1; 62.2 | — |
| SECONDARY PK50 - Mean Residence Time of VWF:Ag |
32.1; 34.3 | — |
| SECONDARY PK50 - Clearance of VWF:Ag |
0.015; 0.015 | — |
| SECONDARY PK50 - Incremental Recovery of VWF:Ag |
2.3; 2.2 | — |
| SECONDARY PK50 - Elimination Phase Half-Life of VWF:Ag |
21.8; 25.2 | — |
| SECONDARY PK50 - Volume of Distribution at Steady State of VWF:Ag |
0.50; 0.49 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB |
80.1; 81.3 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB |
78.7; 75.1 | — |
| SECONDARY PK50 - Mean Residence Time of VWF:CB |
27.5; 26.1 | — |
| SECONDARY PK50 - Clearance of VWF:CB |
0.012; 0.012 | — |
| SECONDARY PK50 - Incremental Recovery of VWF:CB |
3.4; 3.2 | — |
| SECONDARY PK50 - Elimination Phase Half-Life of VWF:CB |
19.3; 18.3 | — |
| SECONDARY PK50 - Volume of Distribution at Steady State of VWF:CB |
0.35; 0.36 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C |
145.4; 113.0 | — |
| SECONDARY PK50 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C |
127.8; 101.8 | — |
| SECONDARY PK50 - Mean Residence Time of FVIII:C |
44.0 | — |
| SECONDARY PK50 - Clearance of FVIII:C |
0.007 | — |
| SECONDARY PK50 - Incremental Recovery of FVIII:C |
2.3 | — |
| SECONDARY PK50 - Elimination Phase Half-Life of FVIII:C |
24.8 | — |
| SECONDARY PK50 - Volume of Distribution at Steady State of FVIII:C |
0.32 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:RCo |
36.9; 38.9 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:RCo |
35.6; 37.9 | — |
| SECONDARY PK80 - Mean Residence Time of VWF:RCo |
26.4; 26.4 | — |
| SECONDARY PK80 - Clearance of VWF:RCo |
0.027; 0.026 | — |
| SECONDARY PK80 - Incremental Recovery of VWF:RCo |
1.8; 1.8 | — |
| SECONDARY PK80 - Elimination Phase Half-Life of VWF:Co |
18.4; 19.8 | — |
| SECONDARY PK80 - Volume of Distribution at Steady State of VWF:RCo |
0.78; 0.75 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:Ag |
66.6; 86.9 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:Ag |
61.3; 77.4 | — |
| SECONDARY PK80 - Mean Residence Time of VWF:Ag |
38.4; 36.9 | — |
| SECONDARY PK80 - Clearance of VWF:Ag |
0.015; 0.012 | — |
| SECONDARY PK80 - Incremental Recovery of VWF:Ag |
2.2; 2.4 | — |
| SECONDARY PK80 - Elimination Phase Half-Life of VWF:Ag |
27.5; 24.8 | — |
| SECONDARY PK80 - Volume of Distribution at Steady State of VWF:Ag |
0.55; 0.50 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of VWF:CB |
73.9; 90.8 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of VWF:CB |
71.9; 88.1 | — |
| SECONDARY PK80 - Mean Residence Time of VWF:CB |
30.9; 28.7 | — |
| SECONDARY PK80 - Clearance of VWF:CB |
0.014; 0.011 | — |
| SECONDARY PK80 - Incremental Recovery of VWF:CB |
3.1; 3.7 | — |
| SECONDARY PK80 - Elimination Phase Half-Life of VWF:CB |
18.8; 20.9 | — |
| SECONDARY PK80 - Volume of Distribution at Steady State of VWF:CB |
0.39; 0.36 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞/Dose) of FVIII:C |
96.8; 94.8 | — |
| SECONDARY PK80 - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours (AUC0-96h/Dose) of FVIII:C |
81.7; 71.8 | — |
| SECONDARY PK80- Ratio of Intra-participant PK of VWF:RCo, VWF:Ag and VWF:CB at Baseline and After 6 Months |
0.9587; 1.0914; 1.0666 | — |
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:
- Type 1 (Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) 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
Data sourced from ClinicalTrials.gov (NCT01410227). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.