Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)

NCT ID: NCT01410227

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-01
• Study Completion Date: 2014-02-01

Brief Summary

The purpose of this Phase 3 study is to assess the pharmacokinetics of rVWF:rFVIII and rVWF, and to assess the safety and efficacy of rVWF:rFVIII and rVWF in the treatment of bleeding events in subjects with severe hereditary von Willebrand disease (VWD).

Conditions

Von Willebrand Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PK 80 Arm (minimum of 22 subjects with severe VWD)

PK assessment (80 IU/kg rVWF) + 12-month treatment period

Group Type: EXPERIMENTAL

Recombinant von Willebrand factor (rVWF)

Intervention Type: BIOLOGICAL

Intravenous administration

Recombinant factor VIIII (rFVIII)

Intervention Type: BIOLOGICAL

Intravenous administration

PK 50 Arm (14 subjects with type 3 VWD)

Two single-blinded PK assessments (50 IU/kg rVWF + rFVIII/placebo) + 12-month treatment period

Group Type: EXPERIMENTAL

Recombinant von Willebrand factor (rVWF)

Intervention Type: BIOLOGICAL

Intravenous administration

Placebo

Intervention Type: DRUG

Syringe supplied with physiologic saline solution for infusion

Recombinant factor VIIII (rFVIII)

Intervention Type: BIOLOGICAL

Intravenous administration

PK 50 Only Arm (minimum of 7 subjects with type 3 VWD)

PK assessment (50 IU/kg rVWF) only, no treatment of bleeding episodes

Group Type: EXPERIMENTAL

Recombinant von Willebrand factor (rVWF)

Intervention Type: BIOLOGICAL

Intravenous administration

Placebo

Intervention Type: DRUG

Syringe supplied with physiologic saline solution for infusion

Recombinant factor VIIII (rFVIII)

Intervention Type: BIOLOGICAL

Intravenous administration

Treatment Only (up to 7 subjects independent of VWD subtype)

Treatment of bleeding episodes for a total of 12 months

Group Type: EXPERIMENTAL

Recombinant von Willebrand factor (rVWF)

Intervention Type: BIOLOGICAL

Intravenous administration

Recombinant factor VIIII (rFVIII)

Intervention Type: BIOLOGICAL

Intravenous administration

Interventions

Recombinant von Willebrand factor (rVWF)

Intravenous administration

Intervention Type: BIOLOGICAL

Placebo

Syringe supplied with physiologic saline solution for infusion

Intervention Type: DRUG

Recombinant factor VIIII (rFVIII)

Intravenous administration

Intervention Type: BIOLOGICAL

Other Intervention Names

BAX 111; rVWF; saline; physiologic saline; rFVIII; ADVATE

Eligibility Criteria

Inclusion Criteria

• Participant has been diagnosed with:

1. Type 1 (Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) < 20 IU/dL) or,

2. Type 2A (VWF:RCo < 20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII activity (FVIII:C) <10% and historically documented genetics), Type 2M or,

3. Type 3 ( Von Willebrand factor antigen (VWF:Ag) ≤ 3 IU/dL) or,

4. Severe Von Willebrand disease (VWD) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding

• Participant, who participates in the treatment for bleeding episodes, has had a minimum of 1 documented bleed (medical history) requiring VWF coagulation factor replacement therapy during the previous 12 months prior to enrollment.
• Participant has a Karnofsky score ≥ 60%
• Participant is at least 18 and not older than 65 years of age at enrollment
• If female of childbearing potential, participant presents with a negative pregnancy test
• Participant 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

Exclusion Criteria

• Participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or elevated PT/international normalized ratio [INR] >1.4).
• Participant has a documented history of a VWF:RCo half-life of <6 hours.
• Participant has a history or presence of a VWF inhibitor at screening.
• Participant has a history or presence of a factor VIII (FVIII) inhibitor with a titer ≥0.4 BU (by Nijmegen assay) or ≥ 0.6 BU (by Bethesda assay).
• Participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
• Participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
• Participant has a medical history of a thromboembolic event.
• Participant is HIV positive with an absolute CD4 count <200/mm3.
• Participant has been diagnosed with cardiovascular disease (New York Heart Association [NYHA] classes 1-4.
• Participant has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, non-seasonal asthma) at screening.
• Participant has been diagnosed with significant liver disease as evidenced by any of the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices).
• Participant has been diagnosed with renal disease, with a serum creatinine level ≥2 mg/dL.
• In the judgment of the investigator, the participant has another clinically significant concomitant disease (eg, uncontrolled hypertension) that may pose additional risks for the participant.
• Participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment
• Participant is pregnant or lactating at the time of enrollment.
• Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study.
• Participant has a history of drug or alcohol abuse within the 2 years prior to enrollment.
• Participant has a progressive fatal disease and/or life expectancy of less than 3 months.
• Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
• Participant suffers from 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.
• Participant is in prison or compulsory detention by regulatory and/or juridical order

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of California Davis Cancer Center

Sacramento, California, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

University of Illinois College of Medicine at Peoria

Peoria, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

The Mary M Gooley Hemophilia Center and Rochester General Hospital

Rochester, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Blood Center of Wisconsin

Milwaukee, Wisconsin, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Medical University Vienna

Vienna, , Austria

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

Specialized Haematological Hospital "Joan Pavel"

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveta Marina"

Varna, , Bulgaria

University of Alberta Hospital

Edmonton, Alberta, Canada

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Gerinnungszentrum Rhein-Ruhr

Duisburg, , Germany

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, , Germany

Jehangir Clinical Development Centre Pvt. Ltd.

Pune, , India

Sahyadri Speciality Hospital

Pune, , India

Christian Medical College

Vellore, , India

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Università degli Studi di Roma "La Sapienza"

Roma, , Italy

Ospedale San Bortolo

Vicenza, , Italy

Nagoya University Hospital

Nagoya, , Japan

Tokyo Medical University Hospital

Tokyo, , Japan

Ogikubo Hospital

Tokyo, , Japan

Erasmus MC

Rotterdam, , Netherlands

UMC Utrecht

Utrecht, , Netherlands

Hematology and Transplantology Clinic, University Clinic Centre - Medical University Hospital

Gdansk, , Poland

Nicolaus Copernicus Provincial Specialist Hospital in Lodz Department of Hematology

Krakow, , Poland

Institute of Haematology and Transfusion Medicine

Warsaw, , Poland

Independent Public Clinical Hospital No. 1 in Wroclaw, Department of Hematology, blood cancer and Bone Marrow Transplantation

Wroclaw, , Poland

Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia

Kirov, , Russia

Territorial Clinical Hospital

Krasnoyarsk, , Russia

Municipal Policlinic # 37

Saint Petersburg, , Russia

Regional Pediatric Clinical Hospital #1

Yekaterinburg, , Russia

Hospital Materno Infantil Teresa Herrera

A Coruña, Galicia, Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario La Paz

Palma de Mallorca, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Skåne University Hospital (SUS)

Malmo, , Sweden

The Royal London Hospital

London, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Bulgaria; Canada; Germany; India; Italy; Japan; Netherlands; Poland; Russia; Spain; Sweden; United Kingdom

References

Gill JC, Castaman G, Windyga J, Kouides P, Ragni M, Leebeek FW, Obermann-Slupetzky O, Chapman M, Fritsch S, Pavlova BG, Presch I, Ewenstein B. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015 Oct 22;126(17):2038-46. doi: 10.1182/blood-2015-02-629873. Epub 2015 Aug 3.

Reference Type: RESULT

PMID: 26239086 (View on PubMed)

Other Identifiers

2010-024108-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

071001

Identifier Type: -

Identifier Source: org_study_id