rVWF IN PROPHYLAXIS

NCT02973087 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 0713012016-001478-14
• Study Type: interventional
• Target: 29
• Locations: 9 countries
• Sites: 35

Brief Summary

The purpose of this phase 3 study is to investigate the efficacy and safety, including immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with severe von Willebrand disease (VWD).

Conditions

Von Willebrand Disease

Outcome Measures

Primary Outcomes (1)

• Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12

  ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).

  Up to 12 months

Secondary Outcomes (64)

• Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12

  Up to 12 months

• Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12

  Up to 12 months

• Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12

  Baseline through Month 12

• Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12

  Up to 12 months

• Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12

  Up to 12 months

Study Arms (1)

All Study Participants

EXPERIMENTAL

Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).

Biological: von Willebrand factor (Recombinant); Biological: Antihemophilic Factor (Recombinant)

Interventions

von Willebrand factor (Recombinant) BIOLOGICAL

OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.

Also known as: BAX 111, rVWF, VONVENDI, vonicog alfa, BAX111

All Study Participants

Antihemophilic Factor (Recombinant) BIOLOGICAL

During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.

Also known as: ADVATE, Recombinant Factor VIII, rFVIII

All Study Participants

Eligibility Criteria

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

You may qualify if:

• Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (\<) 20 International Units/Deciliter \[IU/dL\]) with a history of requiring substitution therapy with von Willebrand factor 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 \[\< or =\] 3 IU/dL).
• Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening.
• For on-demand patient group, participant currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator.
• For Plasma derived von Willebrand factor (pdVWF) product switch patient group, participant has been receiving prophylactic treatment of pdVWF products for no less than 12 months prior to screening.
• For on-demand patient group, participant has greater than or equal to (\>or=) 3 documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand factor (VWF) treatment during the past 12 months.
• Availability of records to reliably evaluate type, frequency and treatment of bleeding episodes during at least 12 months preceding enrollment. Up to 24 months retrospective data should be collected if available. Availability of dosing and factor consumption during 12 months (up to 24 months) of treatment prior to enrollment is required for pdVWF switch participants and is desired (but not a requirement) for on-demand participants.
• Participant is \> or = 18 years old at the time of screening and has a body mass index \> or = 15 but \<40 kilogram per meter square (kg/m\^2).
• If female of childbearing potential, participant presents with a negative blood/urine pregnancy test at screening and 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:

• The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or prothrombin time \[PT\]/international normalized ratio \[INR\] greater than \[\>\]1.4).
• The participant is currently receiving prophylactic treatment with more than 5 infusions per week.
• The participant is currently receiving prophylactic treatment with a weekly dose exceeding 240 IU/kg.
• 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 \> or = 0.6 Bethesda Unit (BU) (by Bethesda assay).
• The participant has a known hypersensitivity to any of the components of the study drugs, such as to 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 millimeter (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 any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices).
• The participant has been diagnosed with renal disease, with a serum creatinine (CR) level \> or = 2.5 milligram 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 (e.g., ointments, nasal sprays), within 30 days prior to signing the informed consent.
• The participant is pregnant or lactating at the time of enrollment.
• Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).

Sponsors & Collaborators

• Takeda: lead
• Baxalta Innovations GmbH, now part of Shire: collaborator

Study Sites (35)

University of Colorado Health

Loveland, Colorado, 80045, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

University of Florida College of Medicine

Jacksonville, Florida, 32610, United States

Location

Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61615, United States

Location

University of Colorado Health

Aurora, Indiana, 80045, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Comprehensive Cancer Center of Wake Forest Unversity

Winston-Salem, North Carolina, 27157, United States

Location

Hamilton Health Sciences Centre

Hamilton, L8N 3Z5, Canada

Location

Hôpital Morvan

Brest, Finistere, 29609, France

Location

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, 69677, France

Location

CHU CAEN - Hôpital de la Côte de Nacre

Caen, 14033, France

Location

CHU Dijon - Hopital du Bocage

Dijon, 21079, France

Location

Hopital Cardiologique - CHU Lille

Lille, 59037, France

Location

Coagulation Research Centre GmbH

Duisburg, 47051, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, 60590, Germany

Location

Werlhof-Institut GmbH

Hanover, 30159, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

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

Roma, 00161, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Erasmus Medisch Centrum

Rotterdam, 3015 AA, Netherlands

Location

SBEI HPE Altai State Medical University of MoH and SD

Barnaul, 656038, Russia

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

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

Kirov, 610027, 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 Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, 34098, 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 Publications (2)

• Hancock JM, Escobar MA. An evaluation of von Willebrand factor (recombinant) therapy for adult patients living with severe type 3 von Willebrand disease. Expert Rev Hematol. 2023 Mar;16(3):157-161. doi: 10.1080/17474086.2023.2184339. Epub 2023 Mar 2.

  PMID: 36861346 DERIVED

• Leebeek FWG, Peyvandi F, Escobar M, Tiede A, Castaman G, Wang M, Wynn T, Baptista J, Wang Y, Zhang J, Mellgard B, Ozen G. Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results. Blood. 2022 Jul 14;140(2):89-98. doi: 10.1182/blood.2021014810.

  PMID: 35439298 DERIVED

Related Links

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

MeSH Terms

Conditions

von Willebrand Diseases

Interventions

von Willebrand Factor; Factor VIII

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; Biological Factors; Protein Precursors

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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: November 16, 2017
• Primary Completion: July 6, 2020
• Study Completion: July 6, 2020
• Last Updated: August 6, 2021
• Results First Posted: August 6, 2021

Record last verified: 2021-08

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

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