A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD)

NCT02932618 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 0711022016-001477-332023-509769-18-00
• Study Type: interventional
• Target: 31
• Locations: 13 countries
• Sites: 46

Brief Summary

The main aim of the study is to check effectiveness, side effects, and tolerability of vonicog alfa (recombinant von Willebrand factor \[rVWF\]), with or without ADVATE, in the treatment and control of nonsurgical bleeding events in pediatric participants (less than (\<)18 years of age) with severe hereditary von Willebrand disease (VWD). The participants will be treated with vonicog alfa for 12-18 months. Their von Willebrand Disease will be treated by their doctor according to their doctor's usual clinical practice. During the study, participants will be followed up at clinics or over telephone calls.

Conditions

Von Willebrand Disease

Outcome Measures

Primary Outcomes (1)

• Hemostatic Efficacy

  Treatment success for vonicog alfa-treated nonsurgical bleeding episodes (using a 4-point scale: Excellent, Good, Moderate, None).

  Within 24 hours after the last infusion of study drug following the onset of the bleeding episode (if/when the severity and/or duration of the bleeding requires the infusion of the study drug)

Secondary Outcomes (25)

• Number of Treated Nonsurgical Bleeding Episodes With an Efficacy Rating of 'Excellent' or 'Good'

  Throughout the study duration of approximately 8.5 years

• Number of Infusions per Bleeding Episode

  Throughout the study duration of approximately 8.5 years

• Number of Vonicog Alfa Units per Bleeding Episode

  Throughout the study duration of approximately 8.5 years

• Number of ADVATE Units (if needed) per Bleeding Episode

  Throughout the study duration of approximately 8.5 years

• Elective or Emergency Surgery: Assessment of Hemostatic Efficacy - Immediately After Surgery

  Immediately after surgery

Study Arms (3)

On-demand Treatment

EXPERIMENTAL

Participants will receive vonicog alfa (recombinant von Willebrand factor \[rVWF\]) treatment for non-surgical bleeding episodes over a 12 to 18-month period.

Biological: Vonicog alfa; Biological: Antihemophilic Factor (Recombinant)

Elective Surgery

EXPERIMENTAL

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.

Biological: Vonicog alfa; Biological: Antihemophilic Factor (Recombinant)

Emergency Surgery

EXPERIMENTAL

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.

Biological: Vonicog alfa; Biological: Antihemophilic Factor (Recombinant)

Interventions

Vonicog alfa BIOLOGICAL

Lyophilized powder and solvent to prepare solution for injection.

Also known as: VONVENDI, rVWF, BAX 111, TAK-577, SHP677

Elective Surgery; Emergency Surgery; On-demand Treatment

Antihemophilic Factor (Recombinant) BIOLOGICAL

Packaged in single boxes with 2 glass vials, with one vial containing the lyophilized ADVATE and the second vial containing the diluent.

Also known as: Recombinant Factor VIII, rFVIII, Octocog alfa

Elective Surgery; Emergency Surgery; On-demand Treatment

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Unable to tolerate are inadequately responsive to, or not a good candidate for 1-deamino-8-D-arginine vasopressin (DDAVP). Examples of participants who are not good candidates for DDAVP include participants with type 2B or type 3 VWD.
• 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.
• \- The participant has not received prior VWF coagulation factor replacement therapy.

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 \[INR\] 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 vonicog alfa 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 vonicog alfa or investigational device during the course of this study.
• Participant's legal representative is a family member or employee of the Investigator.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (46)

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

COMPLETED

University of Florida College of Medicine

Jacksonville, Florida, 32610, United States

RECRUITING

Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61615, United States

RECRUITING

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

COMPLETED

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

COMPLETED

St. Jude Affiliate Clinic at Novant Health

Charlotte, North Carolina, 28204, United States

COMPLETED

Comprehensive Cancer Center of Wake Forest Unversity

Winston-Salem, North Carolina, 27157, United States

COMPLETED

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

COMPLETED

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Texas Children's Cancer and Hematology Center

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, 53225, United States

COMPLETED

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

COMPLETED

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Fakultni nemocnice Brno

Brno, 613 00, Czechia

COMPLETED

Hôpital Morvan

Brest, Finistere, 29609, France

COMPLETED

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, 33000, France

RECRUITING

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, 69677, France

RECRUITING

CHU CAEN - Hôpital de la Côte de Nacre

Caen, 14033, France

RECRUITING

Groupement Hospitalier Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270, France

RECRUITING

Hopital Cardiologique - CHU Lille

Lille, 59037, France

RECRUITING

CHU de Nantes Site Hotel Dieu

Nantes, 44093, France

COMPLETED

Hôpital Necker - Enfants Malades

Paris, 75743, France

RECRUITING

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

COMPLETED

Werlhof-Institut GmbH

Hanover, 30159, Germany

COMPLETED

Medizinische Hochschule Hannover

Hanover, 30625, Germany

COMPLETED

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

RECRUITING

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Azienda Ospedaliera Pediatrica Santobono Pausillipon

Napoli, 80122, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

RECRUITING

Erasmus Medisch Centrum

Rotterdam, 3015 CN, Netherlands

COMPLETED

SBEI HPE Altai State Medical University of MoH and SD

Barnaul, 656038, Russia

COMPLETED

SAIH "Kemerovo Regional Clinical Hospital"

Kemerovo, 650066, Russia

COMPLETED

FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA

Kirov, 610027, Russia

ACTIVE NOT RECRUITING

Hospital General Universitario de Alicante

Alicante, 03010, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

RECRUITING

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

RECRUITING

Ondokuz Mayis Univ. Med. Fac.

Samsun, 55139, Turkey (Türkiye)

RECRUITING

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, 79044, Ukraine

COMPLETED

Royal Manchester Children's Hospital

Manchester, Greater Manchester, M13 9WL, United Kingdom

COMPLETED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

von Willebrand Diseases

Interventions

Factor VIII; F8 protein, human

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

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Central Study Contacts

Takeda Contact

CONTACT

1-877-825-3327; medinfoUS@takeda.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 13, 2016
• Study Start: November 6, 2017
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

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

CZ (1); FR (8); IT (4); NL (1); UA (1); BE (1); US (16); GB (1); DE (3); RU (3); AU (2); ES (2); TU (3)