A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD)

NCT03879135 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: SHP677-3042018-003453-16
• Study Type: interventional
• Target: 38
• Locations: 9 countries
• Sites: 33

Brief Summary

The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not related to trauma) bleeding episodes in pediatric and adult participants during the first 12 months on study treatment. The participants will be treated with rVWF for a maximum of 3 years. Their von Willebrand Disease will be treated according to Investigational product (IP) dosing directions.

Conditions

Von Willebrand Disease (VWD)

Outcome Measures

Primary Outcomes (1)

• Spontaneous Annualized Bleeding Rate (sABR)

  sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during the first 12 months of prophylactic treatment with rVWF (vonicog alfa) was reported.

  Up to 12 months

Secondary Outcomes (29)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  Up to 5.8 years

• Number of Participants Based on Severity of TEAEs

  Up to 5.8 years

• Number of Participants Based on Causality of TEAEs

  Up to 5.8 years

• Number of Participants With Thromboembolic Events

  Up to 5.8 years

• Number of Participants With Hypersensitivity Reactions

  Up to 5.8 years

Study Arms (2)

On-Demand

EXPERIMENTAL

Participants will receive recombinant von Willebrand factor (rVWF) (with or without ADVATE).

Biological: rVWF; Biological: rFVIII

Prophylaxis

EXPERIMENTAL

Participants will receive recombinant von Willebrand factor (rVWF).

Biological: rVWF; Biological: rFVIII

Interventions

rVWF BIOLOGICAL

Recombinant von Willebrand factor

Also known as: Vonvendi, Vonicog alfa

On-Demand; Prophylaxis

rFVIII BIOLOGICAL

Recombinant Factor VIII

Also known as: Octocog alfa, ADVATE

On-Demand; Prophylaxis

Eligibility Criteria

• Age: 0 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant will not be considered eligible for the study without meeting all of the criteria below.
• Participants who have completed Study 071301 or Study 071102 (or participants who have completed the surgery arm treatment in Study 071102 and want to continue to receive on-demand (OD) treatment) and are willing to immediately transition into this study, must meet the following 2 criteria to be eligible for this study:
• If female of childbearing potential, has a negative blood/urine pregnancy test at screening and agrees to employ highly effective birth control measures for the duration of the study.
• Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
• New participants (Cohort 4) who meet the above 2 and ALL the following additional criteria are eligible for this study:
• \- Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline von Willebrand factor: Ristocetin cofactor (VWF:RCo) \<20 International Units per deciliter \[IU/dL\]) with a history of requiring substitution therapy with von Willebrand factor (vWF) concentrate to control bleeding:
• Type 1 (VWF:RCo \<20 IU/dL) or,
• Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,
• Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to (\<=) 3 IU/dL).
• Diagnosis is confirmed by genetic testing and multimer analysis, documented in participant history or at screening.
• Participant has been receiving OD therapy with VWF products for at least 12 months, and prophylactic treatment is recommended by the investigator.
• Participant has greater than or equal to (\>=) 3 documented spontaneous bleeds (not including menorrhagia) requiring VWF treatment during the past 12 months.
• Participant has available records that reliably evaluate type, frequency, and treatment of bleeding episodes for at least 12 months preceding enrollment; up to 24 months of retrospective data should be collected if available.
• Participant is \>=12 years old at the time of screening and has a body mass index \>=15 but \<40 kilogram per meter square (kg/m\^2).

You may not qualify if:

• The participant has been diagnosed with Type 2N VWD, pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg, qualitative and quantitative platelet disorders or elevated prothrombin time (PT)/international normalized ratio \[INR\] \>1.4).
• The participant has a history or presence of a VWF inhibitor at screening.
• The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer \>=0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or \>=0.6 BU (by Bethesda assay).
• The participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
• The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or animal allergies.
• The participant has a medical history of a thromboembolic event.
• The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count \<200/cubic millimeters (mm\^3).
• The participant has been diagnosed with significant liver disease per investigator's medical assessment of the participant's current condition or medical history or as evidenced by, but not limited to any of the following: serum alanine aminotransferase (ALT) greater than 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-Pugh class B or C.
• The participant has been diagnosed with renal disease, with a serum creatinine (CR) level \>=2.5 milligrams per deciliter (mg/dL).
• The participant has a platelet count \<100,000/milliliter (mL) at screening.
• The participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent (or assent, if appropriate).
• The participant is pregnant or lactating at the time of enrollment.
• The participant has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
• The participant has participated in another clinical study involving another investigational product (IP) 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.
• The participant has a progressive fatal disease and/or life expectancy of less than 15 months.

Sponsors & Collaborators

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

Study Sites (33)

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, 72202, United States

Location

University of Colorado Health

Aurora, Colorado, 80045, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

AKH - Medizinische Universität Wien

Vienna, Austria

Location

Hopital Cardiologique - CHU Lille

Lille, Nord, France

Location

Hôpital Necker - Enfants Malades

Paris, Paris, 75015, France

Location

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, 69677, France

Location

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Gironde, France

Location

Groupement Hospitalier Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, Germany

Location

Werlhof-Institut GmbH

Hanover, Germany

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Azienda Ospedaliera Pediatrica Santobono Pausillipon

Napoli, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Roma, 00185, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

Erasmus Medisch Centrum

Rotterdam, 3015 AA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CN, Netherlands

Location

SAIH "Kemerovo Regional Clinical Hospital"

Kemerovo, 650066, Russia

Location

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

Kirov, 610017, Russia

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Istanbul University Oncology Institute

Istanbul, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35040, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Ondokuz Mayis Univ. Med. Fac.

Samsun, 55139, Turkey (Türkiye)

Location

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

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: March 18, 2019
• Study Start: April 1, 2019
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: September 3, 2025
• Results First Posted: September 3, 2025

Record last verified: 2025-08

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

IT (6); US (8); FR (5); AU (1); RU (2); TU (4); DE (2); NL (2); ES (3)