rVWF IN PROPHYLAXIS

NCT ID: NCT02973087

Last Updated: 2021-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-16
• Study Completion Date: 2020-07-06

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

All Study Participants

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).

Group Type: EXPERIMENTAL

von Willebrand factor (Recombinant)

Intervention Type: 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.

Antihemophilic Factor (Recombinant)

Intervention Type: 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.

Interventions

von Willebrand factor (Recombinant)

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.

Intervention Type: BIOLOGICAL

Antihemophilic Factor (Recombinant)

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

BAX 111; rVWF; VONVENDI; vonicog alfa; BAX111; ADVATE; Recombinant Factor VIII; rFVIII

Eligibility Criteria

Inclusion Criteria

1. 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

1. Type 1 (VWF:RCo <20 IU/dL) or,

2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,

3. Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to [< or =] 3 IU/dL).

2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening.

3. For on-demand patient group, participant currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator.

4. 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.

5. 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.

6. 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.

7. 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).

8. 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.

9. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

1. 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).

2. The participant is currently receiving prophylactic treatment with more than 5 infusions per week.

3. The participant is currently receiving prophylactic treatment with a weekly dose exceeding 240 IU/kg.

4. The participant has a history or presence of a VWF inhibitor at screening.

5. 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).

6. The participant has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.

7. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.

8. The participant has a medical history of a thromboembolic event.

9. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count <200/ cubic millimeter (mm^3).

10. 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).

11. The participant has been diagnosed with renal disease, with a serum creatinine (CR) level > or = 2.5 milligram per deciliter (mg/dL).

12. The participant has a platelet count <100,000/ milliliter (mL) at screening.

13. 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.

14. The participant is pregnant or lactating at the time of enrollment.

15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).

16. 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.

17. The participant has a progressive fatal disease and/or life expectancy of less than 15 months.

18. The participant is scheduled for a surgical intervention.

19. The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.

20. The participant has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.

21. The participant is in prison or compulsory detention by regulatory and/or juridical order.

22. The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta Innovations GmbH, now part of Shire

INDUSTRY

Sponsor Role: collaborator

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Colorado Health

Loveland, Colorado, United States

University of Florida College of Medicine

Gainesville, Florida, United States

University of Florida College of Medicine

Jacksonville, Florida, United States

Bleeding and Clotting Disorders Institute

Peoria, Illinois, United States

University of Colorado Health

Aurora, Indiana, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

Henry Ford Hospital

Detroit, Michigan, United States

Comprehensive Cancer Center of Wake Forest Unversity

Winston-Salem, North Carolina, United States

Hamilton Health Sciences Centre

Hamilton, , Canada

Hôpital Morvan

Brest, Finistere, France

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, , France

CHU CAEN - Hôpital de la Côte de Nacre

Caen, , France

CHU Dijon - Hopital du Bocage

Dijon, , France

Hopital Cardiologique - CHU Lille

Lille, , France

Coagulation Research Centre GmbH

Duisburg, , Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, , 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 Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Roma, , Italy

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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

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 Universitario La Paz

Madrid, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Countries

United States; Canada; France; Germany; Italy; Netherlands; Russia; Spain; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 36861346 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35439298 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b5fc34db2bf003ab45955

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

Other Identifiers

2016-001478-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

071301

Identifier Type: -

Identifier Source: org_study_id