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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02283268




Registration number
NCT02283268
Ethics application status
Date submitted
27/10/2014
Date registered
5/11/2014

Titles & IDs
Public title
Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery
Scientific title
A Phase 3, Prospective, Multicenter Study to Evaluate Efficacy and Safety of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Elective Surgical Procedures in Subjects With Severe Von Willebrand Disease
Secondary ID [1] 0 0
2014-003575-38
Secondary ID [2] 0 0
071101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Von Willebrand Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Recombinant von Willebrand Factor (rVWF)

Experimental: Recombinant von Willebrand Factor (rVWF) - Surgery participants treated with Recombinant von Willebrand Factor (rVWF)


Treatment: Other: Recombinant von Willebrand Factor (rVWF)
rVWF will be administered by intravenous bolus infusion. Participants planned for major surgery will undergo a baseline pharmacokinetic assessment prior to surgery. The peri- and postoperative substitution regimen will be individualized according to the PK results, intensity and duration of the hemostatic challenge, and the institution´s standard of care.

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician)
Timepoint [1] 0 0
24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier
Secondary outcome [1] 0 0
Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon
Timepoint [1] 0 0
Day 0 (at completion of surgery)
Secondary outcome [2] 0 0
Intraoperative Actual Blood Loss Relative to Predicted Blood Loss
Timepoint [2] 0 0
Day 0 (at completion of surgery)
Secondary outcome [3] 0 0
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon
Timepoint [3] 0 0
Day 0 (at completion of surgery)
Secondary outcome [4] 0 0
Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon
Timepoint [4] 0 0
Day 0 (at completion of surgery)
Secondary outcome [5] 0 0
Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE
Timepoint [5] 0 0
Daily, from day of surgery through postoperative Day 14 (± 2 days)
Secondary outcome [6] 0 0
Occurrence of Adverse Events
Timepoint [6] 0 0
From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)
Secondary outcome [7] 0 0
Occurrence of Thrombotic Events
Timepoint [7] 0 0
From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)
Secondary outcome [8] 0 0
Occurrence of Severe Allergic Reactions (eg, Anaphylaxis)
Timepoint [8] 0 0
From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery)
Secondary outcome [9] 0 0
Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII)
Timepoint [9] 0 0
Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).
Secondary outcome [10] 0 0
Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) or Recombinant Furin (rFurin)
Timepoint [10] 0 0
Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).
Secondary outcome [11] 0 0
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose)
Timepoint [11] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [12] 0 0
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-8 /Dose)
Timepoint [12] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [13] 0 0
Pharmacokinetics: Mean Residence Time (MRT)
Timepoint [13] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [14] 0 0
Pharmacokinetics: Clearance (CL)
Timepoint [14] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [15] 0 0
Pharmacokinetics: Incremental Recovery (IR)
Timepoint [15] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [16] 0 0
Pharmacokinetics: Elimination Phase Half-life (T1/2)
Timepoint [16] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.
Secondary outcome [17] 0 0
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Timepoint [17] 0 0
PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Eligibility
Key inclusion criteria
* Diagnosis of severe von Willebrand disease (VWD) as listed below and elective surgical procedure planned

1. Type 1 (Von Willebrand factor : Ristocetin cofactor activity (VWF:RCo) <20 IU/dL), or
2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2N (FVIII:C<10% and historically documented genetics), Type 2M, or
3. Type 3 (Von Willebrand factor antigen (VWF:Ag) = 3 IU/dL)
* VWD with a history of requiring substitution therapy with von Willebrand factor (VWF) concentrate to control bleeding
* If type 3 VWD (VWF Antigen /VWF:Ag = 3 IU/dL), participant has a medical history of at least 20 exposure days to VWF/FVIII coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma)
* If type 1 or type 2 VWD, participant has a medical history of 5 exposure days or a past major surgery requiring VWF/FVIII coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma)
* Participant is at least 18 years of age
* If female of childbearing potential, participant presents with a negative pregnancy test
* If applicable, 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Diagnosis of pseudo VWD or another hereditary or acquired coagulation disorder (eg, qualitative and quantitative platelet disorders or elevated prothrombin time [PT] / international normalized ratio [INR] > 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Perth Blood Institute - Nedlands
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Czechia
State/province [13] 0 0
Ostrava
Country [14] 0 0
Germany
State/province [14] 0 0
Rheinland-Pfalz
Country [15] 0 0
Italy
State/province [15] 0 0
Firenze (Florence)
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Italy
State/province [17] 0 0
Rome
Country [18] 0 0
Netherlands
State/province [18] 0 0
Rotterdam
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Barnaul
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Kirov
Country [21] 0 0
Spain
State/province [21] 0 0
A Coruña
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taichung
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taipei
Country [25] 0 0
Turkey
State/province [25] 0 0
Izmir
Country [26] 0 0
Ukraine
State/province [26] 0 0
Lviv
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Devon
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Greater London
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Oxfordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Baxalta now part of Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.