Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery

NCT ID: NCT02283268

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-01
• Study Completion Date: 2016-07-06

Brief 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).

Conditions

Von Willebrand Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Recombinant von Willebrand Factor (rVWF)

Surgery participants treated with Recombinant von Willebrand Factor (rVWF)

Group Type: EXPERIMENTAL

Recombinant von Willebrand Factor (rVWF)

Intervention Type: BIOLOGICAL

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.

Interventions

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 Type: BIOLOGICAL

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, United States

University of Miami, Jackson Memorial Hospital

Miami, Florida, United States

Georgia Regents University

Augusta, Georgia, United States

John Hopkins University

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

Case Western Reserve University Hospital

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Blood Center of South East Wisconsin

Milwaukee, Wisconsin, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Perth Blood Institute

Nedlands, Western Australia, Australia

Fiona Stanley Hospital

Perth, Western Australia, Australia

AKH - Medizinische Universität Wien

Vienna, , Austria

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Azienda Ospedaliero - Universitaria Careggi

Firenze (Florence), , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Umberto I Policlinico di Roma, Universitá di Roma La Sapienza

Rome, , Italy

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Regional Budgetary State Healthcare Institution (SHI) "Regional Clinical Hospital"

Barnaul, , Russia

FSI Kirov Institute of Hematology and Blood Transfusion FMBA

Kirov, , Russia

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Taichung Veterans General Hospital

Taichung, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, , Ukraine

Derriford Hospital

Plymouth, Devon, United Kingdom

Royal Free Hospital

London, Greater London, United Kingdom

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Countries

United States; Australia; Austria; Czechia; Germany; Italy; Netherlands; Russia; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

2014-003575-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

071101

Identifier Type: -

Identifier Source: org_study_id