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

NCT02283268 | Completed Phase 3 Results DMC

• 2 other identifiers: 0711012014-003575-38
• Study Type: interventional
• Target: 24
• Locations: 12 countries
• Sites: 33

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

Outcome Measures

Primary Outcomes (1)

• Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician)

  Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intra-, and postoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intra-, and postoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intra-, and postoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

  24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier

Secondary Outcomes (17)

• Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon

  Day 0 (at completion of surgery)

• Intraoperative Actual Blood Loss Relative to Predicted Blood Loss

  Day 0 (at completion of surgery)

• Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon

  Day 0 (at completion of surgery)

• Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon

  Day 0 (at completion of surgery)

• Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE

  Daily, from day of surgery through postoperative Day 14 (± 2 days)

Study Arms (1)

Recombinant von Willebrand Factor (rVWF)

EXPERIMENTAL

Surgery participants treated with Recombinant von Willebrand Factor (rVWF)

Biological: Recombinant von Willebrand Factor (rVWF)

Interventions

Recombinant von Willebrand Factor (rVWF) 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.

Recombinant von Willebrand Factor (rVWF)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \<20 IU/dL), or
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (34)

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, 80045, United States

Location

University of Miami, Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

John Hopkins University

Baltimore, Maryland, 21205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Case Western Reserve University Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Blood Center of South East Wisconsin

Milwaukee, Wisconsin, 53233, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Perth Blood Institute

Nedlands, Western Australia, 6009, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6000, Australia

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

Fakultni nemocnice Ostrava

Ostrava, 70852, Czechia

Location

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, 55101, Germany

Location

Azienda Ospedaliero - Universitaria Careggi

Firenze (Florence), 50139, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Umberto I Policlinico di Roma, Universitá di Roma La Sapienza

Rome, 00144, Italy

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CE, Netherlands

Location

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

Barnaul, 656024, Russia

Location

FSI Kirov Institute of Hematology and Blood Transfusion FMBA

Kirov, 610027, Russia

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Tri-Service General Hospital

Taipei, 10002, Taiwan

Location

National Taiwan University Hospital

Taipei, 11490, Taiwan

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, 79044, Ukraine

Location

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Royal Free Hospital

London, Greater London, NW3 2QG, United Kingdom

Location

Churchill Hospital

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

von Willebrand Diseases

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: November 5, 2014
• Study Start: April 1, 2015
• Primary Completion: July 6, 2016
• Study Completion: July 6, 2016
• Last Updated: May 19, 2021
• Results First Posted: August 31, 2017

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: 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.

Locations

TU (1); AU (3); CZ (1); US (12); IT (3); NL (1); RU (2); TW (3); UA (1); GB (3); DE (1); ES (2)