Phase 3
N=15
Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery
Von Willebrand Disease
Bottom Line
View on ClinicalTrials.gov: NCT02283268 ↗Enrolled (actual)
15
Serious AEs
13.3%
Results posted
Aug 2017
Primary outcome: Primary: Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) — 11; 4; 7; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Recombinant von Willebrand Factor (rVWF) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician) |
11; 4; 7; 0; 2; 1 | — |
| SECONDARY Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon |
94.3; 0.0; 127.0; 145.0; 115.0; 42.5 | — |
| SECONDARY Intraoperative Actual Blood Loss Relative to Predicted Blood Loss |
69.6; 0.0; 68.9; 145.0; 122.5; 50.0 | — |
| SECONDARY Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon |
13; 4; 8; 1; 3; 1 | — |
| SECONDARY Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon |
13; 4; 8; 1; 3; 1 | — |
| SECONDARY Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE |
18.1; 23.5; 42.3; 28.6; 33.9; 31.5 | — |
| SECONDARY Occurrence of Adverse Events |
12; 1; 0; 0; 0; 2 | — |
| SECONDARY Occurrence of Thrombotic Events |
2; 1 | — |
| SECONDARY Occurrence of Severe Allergic Reactions (eg, Anaphylaxis) |
0; 0 | — |
| SECONDARY Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII) |
0; 1; 0 | — |
| SECONDARY Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) or Recombinant Furin (rFurin) |
— | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose) |
31.91; 57.08; 63.91; 54.61; 67.49 | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose) |
34.43; 68.87; 71.82; 61.90; 75.00 | — |
| SECONDARY Pharmacokinetics: Mean Residence Time (MRT) |
22.69; 37.92; 29.35; 29.75 | — |
| SECONDARY Pharmacokinetics: Clearance (CL) |
0.02904; 0.01452; 0.01392; 0.01616 | — |
| SECONDARY Pharmacokinetics: Incremental Recovery (IR) |
1.961; 1.991; 2.780; 2.635 | — |
| SECONDARY Pharmacokinetics: Elimination Phase Half-life (T1/2) |
16.52; 26.88; 21.07; 22.19 | — |
| SECONDARY Pharmacokinetics: Volume of Distribution at Steady State (Vss) |
0.6591; 0.5506; 0.4086; 0.4806 | — |
Summary
The purpose of the study is to assess the efficacy and safety of recombinant von Willebrand factor (rVWF) with or without ADVATE in major and minor elective surgical procedures in adult patients with hereditary severe von Willebrand disease (VWD).
Eligibility Criteria
Inclusion Criteria
- Diagnosis of severe von Willebrand disease (VWD) as listed below and elective surgical procedure planned
- Type 1 (Von Willebrand factor : Ristocetin cofactor activity (VWF:RCo) 1.4)
- History or presence of a VWF inhibitor at screening
- History or presence of a factor VIII (FVIII) inhibitor with a titer ≥ 0.4 BU (Nijmegen-modified Bethesda assay ) or ≥ 0.6 BU (by Bethesda assay)
- Known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins
- Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies
- Medical history of a thromboembolic event
- HIV positive with an absolute CD4 count < 200/mm3
- Platelet count < 100,000/mL
- Diagnosis of significant liver disease, as evidenced by, but not limited to, 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) or liver cirrhosis classified as Child B or C
- Diagnosis of renal disease, with a serum creatinine level ≥ 2 .5mg/dL
- Participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent
- Participant is pregnant or lactating at the time informed content is obtained
- Participant has participated in another clinical study involving an investigational product (IP), other than rVWF with or without ADVATE, 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. However, eligible patients participating in the rVWF Prophylaxis Study (071301) may be enrolled.
- 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
- Participant is a member of the study team conducting this study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees.
Data sourced from ClinicalTrials.gov (NCT02283268). 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.