A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD)
Von Willebrand Disease
About this trial
This is an interventional treatment trial for Von Willebrand Disease
Eligibility Criteria
Inclusion Criteria:
Diagnosis of severe von Willebrand disease (VWD) (defined as von Willebrand factor: ristocetin cofactor [VWF:RCo] less than [<] 20 percent [%]):
- Type 1 (VWF:RCo <20 International Units per deciliter [IU/dL]); or
- Type 2A (VWF:RCo <20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII coagulation activity [FVIII:C] <10 % and historically documented genetics), Type 2M; or
- Type 3 (VWF:Ag less than or equal to [=<] 3 IU/dL).
- Age 0 to <18 years at the time of Screening.
- The participant has provided assent (if appropriate) and legally authorized representative(s) has provided informed consent.
- If female of childbearing potential, participant presents with a negative serum pregnancy test.
- If applicable, participant agrees to employ adequate birth control measures for the duration of the study.
- The participant and/or the legally authorized representative are willing and able to comply with the requirements of the protocol, which should also be confirmed based on a pre-screening evaluation held between the Investigator and the Sponsor, to ensure no eminent risk is present that could challenge the participants compliance with the study requirements.
Additional inclusion criteria for both previously treated participants and participants undergoing surgery are as follows:
- Unable to tolerate or are inadequately responsive to deamino-delta-D-arginine vasopressin (DDAVP).
- The participant has had a minimum of 1 documented bleed requiring VWF coagulation factor replacement therapy (i.e. treatment with a VWF product) during the previous 12 months prior to enrollment and overall historically 3 or more exposure days (EDs) to VWF replacement therapy.
Additional inclusion criterion for previously untreated participants are as follows:
- The participant has not received prior VWF coagulation factor replacement therapy.
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] greater than [>] 1.4).
- History or presence of a VWF inhibitor at Screening.
- History or presence of a Factor VIII (FVIII) inhibitor with a titer greater than or equal [>=] 0.4 Bethesda units (BU) (by Nijmegen assay) or >=0.6 BU (by Bethesda assay).
- Documented history of a VWF: RCo half-life <6 hours.
- Known hypersensitivity to any of the components of the study drug, such as mouse or hamster proteins.
- Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/asthma, food allergies, or animal allergies.
- Medical history of a thromboembolic event.
- Human immunodeficiency virus (HIV) positive, with an absolute CD4 count <200/ cubic millimeter (mm^3).
- In the judgment of the Investigator, the participant has another clinically significant concomitant disease (e.g. uncontrolled hypertension, cancer) that may pose additional risks for the participant.
- Diagnosis of significant liver disease, as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) of 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g. 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 >=2.5 milligram per deciliter (mg/dL).
- Immunomodulatory drug treatment other than anti-retroviral chemotherapy (e.g. α-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 milligram per day [mg/day] (excluding topical treatment [e.g. ointments, nasal sprays]), within 30 days prior to signing the informed consent (or assent, if appropriate).
- If female, participant is pregnant or lactating at the time informed consent (or assent, if appropriate) 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 other than rVWF or investigational device during the course of this study.
- Participant's legal representative is a family member or employee of the Investigator.
Sites / Locations
- University of Colorado Hemophilia & Thrombosis CenterRecruiting
- Children's National Medical Center
- University of Florida College of MedicineRecruiting
- Bleeding and Clotting Disorders InstituteRecruiting
- Indiana Hemophilia and Thrombosis Center
- University of Nebraska Medical Center
- St. Jude Affiliate Clinic at Novant Health
- Comprehensive Cancer Center of Wake Forest Unversity
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Children's HospitalRecruiting
- Nationwide Children's HospitalRecruiting
- Children's Hospital of Philadelphia
- Medical University of South CarolinaRecruiting
- Texas Children's Cancer and Hematology CenterRecruiting
- Texas Children's HospitalRecruiting
- Comprehensive Center for Bleeding Disorders
- Medizinische Universität Innsbruck
- AKH - Medizinische Universität WienRecruiting
- UZ LeuvenRecruiting
- Fakultni nemocnice Brno
- Hôpital Morvan
- Groupe Hospitalier Pellegrin - Hôpital PellegrinRecruiting
- Groupement Hospitalier Est- Hôpital Louis PradelRecruiting
- CHU CAEN - Hôpital de la Côte de NacreRecruiting
- Groupement Hospitalier Sud - Hôpital BicêtreRecruiting
- Hopital Cardiologique - CHU LilleRecruiting
- CHU de Nantes Site Hotel Dieu
- Hôpital Necker - Enfants MaladesRecruiting
- Universitaetsklinikum Hamburg-Eppendorf
- Werlhof-Institut GmbH
- Medizinische Hochschule Hannover
- Azienda Ospedaliera Universitaria CareggiRecruiting
- Fondazione IRCCS CA' Granda Ospedale Maggiore PoliclinicoRecruiting
- Azienda Ospedaliera Pediatrica Santobono PausilliponRecruiting
- Ospedale Pediatrico Bambino GesùRecruiting
- Erasmus Medisch Centrum
- SBEI HPE Altai State Medical University of MoH and SD
- SAIH "Kemerovo Regional Clinical Hospital"
- FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA
- Hospital General Universitario de AlicanteRecruiting
- Hospital Universitari i Politecnic La FeRecruiting
- Istanbul University Cerrahpasa Medical FacultyRecruiting
- Ege University Medical FacultyRecruiting
- Ondokuz Mayis Univ. Med. Fac.Recruiting
- SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
- Royal Manchester Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
On-demand Treatment
Elective Surgery
Emergency Surgery
Participants will receive recombinant von Willebrand factor (rVWF) treatment for non-surgical bleeding episodes over a 12 to 18-month period.
12-24 hours prior to surgery and within 3 hours of surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours based on post-operative dosing. Oral Surgery: infuse at least once within first 8-12 hours post-surgery based on post-operative dosing. Major Surgery: infuse every 12-24 hours for at least first 96 hours post-surgery based on post-operative dosing.
Within 3 hours prior to surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours based on post-operative dosing. Oral Surgery: infuse at least once within first 8-12 hours post-surgery based on post-operative dosing. Major Surgery: infuse every 12-24 hours for at least first 96 hours post-surgery based on post-operative dosing.