RecruitingPhase 3NCT02932618

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

A Phase 3, Prospective, Multicenter, Uncontrolled, Open-Label Clinical Study to Determine the Efficacy, Safety, and Tolerability of rVWF With or Without ADVATE in the Treatment and Control of Bleeding Episodes, the Efficacy and Safety of rVWF in Elective and Emergency Surgeries, and the Pharmacokinetics (PK) of rVWF in Children Diagnosed With Severe Von Willebrand Disease


Sponsor

Baxalta now part of Shire

Enrollment

31 participants

Start Date

Nov 6, 2017

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Max Age: 17 Years

Inclusion Criteria13

  • 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.
  • Additional inclusion criterion for previously untreated participants are as follows:
  • \- The participant has not received prior VWF coagulation factor replacement therapy.

Exclusion Criteria15

  • 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.

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Interventions

BIOLOGICALVonicog alfa

Lyophilized powder and solvent to prepare solution for injection.

BIOLOGICALAntihemophilic Factor (Recombinant)

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


Locations(46)

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, United States

Children's National Medical Center

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

University of Florida College of Medicine

Jacksonville, Florida, United States

Bleeding and Clotting Disorders Institute

Peoria, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

St. Jude Affiliate Clinic at Novant Health

Charlotte, North Carolina, United States

Comprehensive Cancer Center of Wake Forest Unversity

Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Children's Cancer and Hematology Center

Houston, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, United States

Medizinische Universität Innsbruck

Innsbruck, Austria

AKH - Medizinische Universität Wien

Vienna, Austria

UZ Leuven

Leuven, Belgium

Fakultni nemocnice Brno

Brno, Czechia

Hôpital Morvan

Brest, Finistere, France

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, France

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, France

CHU CAEN - Hôpital de la Côte de Nacre

Caen, France

Groupement Hospitalier Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, France

Hopital Cardiologique - CHU Lille

Lille, France

CHU de Nantes Site Hotel Dieu

Nantes, France

Hôpital Necker - Enfants Malades

Paris, France

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, Germany

Werlhof-Institut GmbH

Hanover, Germany

Medizinische Hochschule Hannover

Hanover, Germany

Azienda Ospedaliera Universitaria Careggi

Florence, Italy

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, Italy

Azienda Ospedaliera Pediatrica Santobono Pausillipon

Naples, Italy

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Erasmus Medisch Centrum

Rotterdam, Netherlands

SBEI HPE Altai State Medical University of MoH and SD

Barnaul, Russia

SAIH "Kemerovo Regional Clinical Hospital"

Kemerovo, Russia

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

Kirov, Russia

Hospital General Universitario de Alicante

Alicante, Spain

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Istanbul University Cerrahpasa Medical Faculty

Istanbul, Turkey (Türkiye)

Ege University Medical Faculty

Izmir, Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, Turkey (Türkiye)

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

Lviv, Ukraine

Royal Manchester Children's Hospital

Manchester, Greater Manchester, United Kingdom

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NCT02932618


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