Pharmacokinetic, Safety and Tolerability Study of Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex in Type 3 Von Willebrand Disease

Phase 1

Completed

• Conditions: Von Willebrand Disease
• Interventions: Biological: Marketed plasma-derived VWF/FVIII concentrate

• Registration Number: NCT00816660
• Lead Sponsor: Baxalta now part of Shire

Brief Summary

The objectives of this study are to evaluate the immediate tolerability and safety of rVWF:rFVIII in subjects with Type 3 Von Willebrand Disease after administration of various dosages of VWF:RCo.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-01
• Study First Submitted: 2009-01-02
• Study First Submitted QC: 2009-01-02
• Study First Posted: 2009-01-05
• Primary Completion: 2010-08-31
• Study Completion: 2010-08-31
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-29
• Last Update Posted: 2021-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Subject has voluntarily given written informed consent (before conduct of any study-related procedures)
• The subject has hereditary type 3 VWD (<= 3 IU/dL VWF:Ag)or severe type 1 or type 2A VWD (VWF:RCo <= 10% and FVIII:C <20%)
• The subject has a medical history of at least 25 exposure days to VWF/FVIII coagulation factor concentrates
• The subject has a Karnofsky score >= 70%
• The subject is between 18 to 60 years of age (on the day of signing the informed consent)
• NOT APPLICABLE IN ITALY: Female subjects of child-bearing potential must have a negative pregnancy test and agree to practice contraception using a method of proven reliability from the day of screening until the study completion visit
• APPLICABLE ONLY IN ITALY: Female subjects of child-bearing potential must have a negative pregnancy test and agree to practice non-hormonal-based contraception using a method of proven reliability (IUD acceptable) from the day of screening until 96 hours after the last investigational drug infusion
• NOT APPLICABLE IN ITALY: The subject must agree not to be on any therapy (hormone-based contraception acceptable) interfering with coagulation factor pharmacokinetics until 96 hours after the last investigational drug infusion
• APPLICABLE ONLY IN ITALY: The subject must agree not to be on any therapy interfering with coagulation factor pharmacokinetics until 96 hours after the last investigational drug infusion

Exclusion Criteria

• The subject has been diagnosed with a hereditary or acquired coagulation disorder other than VWD (including qualitative and quantitative platelet disorders and/or an international normalized ratio (INR) > 1.4)
• The subject has been diagnosed with an ADAMTS13 deficiency with less than 10% ADAMTS13 activity
• The subject has a history or presence of VWF inhibitor
• The subject has a history or presence of FVIII inhibitor with a titer >= 0.4 BU (by Nijmegen assay) or >= 0.6 BU (by Bethesda assay)
• The subject has a known hypersensitivity to mouse or hamster proteins
• The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, food allergies or animal allergies
• The subject has a medical history of a thromboembolic event
• The subject is HIV positive with an absolute CD4 count < 200/mm3
• The subject has been diagnosed with cardiovascular disease (New York Heart Association (NYHA) classes 1-4)
• The subject has been diagnosed with insulin-dependent diabetes mellitus
• The subject has an acute illness (e.g. influenza, flu-like syndrome, allergic rhinitis/conjunctivitis)
• The subject has been diagnosed with liver disease, as evidenced by, but not limited to, any of the following: serum ALT three times the upper limit of normal, hypoalbuminemia, portal vein hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices)
• The subject has been diagnosed with renal disease, with a serum creatinine level >= 2 mg/dL
• In the judgment of the investigator, the subject has another clinically significant concomitant disease (e.g. uncontrolled hypertension, diabetes type II) that may pose additional risks for the subject
• The subject has been treated with an immunomodulatory drug, excluding topical treatment (e.g. ointments, nasal sprays) within 30 days before enrollment
• The subject has been treated with drugs known to induce thrombotic thrombocytopenic purpura (TTP) (e.g. Adenosine diphosphate (ADP) receptor inhibitors (Clopidogrel, Ticlopidine)) within 60 days before enrollment
• The subject is receiving or anticipates receiving another investigational and/or interventional drug within 30 days before enrollment
• The subject is a lactating female
• The subject has a history of drug or alcohol abuse within the last 5 years
• The subject has a progressive fatal disease and/or life expectancy of less than 3 months
• The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures
• The subject 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
• Subject is in prison or compulsory detention by regulatory and/or juridical order

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
2	Marketed plasma-derived VWF/FVIII concentrate	-

Primary Outcome Measures

Name	Time	Method
To demonstrate the immediate tolerability and safety after single-dose injections of rVWF:rFVIII at various doses	Up to 30 days after the last investigational product infusion

Trial Locations

Locations (25)

Ospedale di Vicenza - U.L.S.S.N.6; 🇮🇹 Vicenza, Italy

Brigham & Women´s Hospital, Hematology Division; 🇺🇸 Boston, Massachusetts, United States

General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien), University Department for Internal Medicine I; 🇦🇹 Vienna, Austria

Institut für Thrombophilie und Hämostaseologie; 🇩🇪 Münster, Germany

Azienda Ospedaliero-universitaria "Careggi"; 🇮🇹 Firenze, Italy

Giannia Gaslini Children´s Hospital; 🇮🇹 Genova, Italy

Ospedale Maggiore di Milano, Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"; 🇮🇹 Milan, Italy

Emory University School of Medicine, Dept. of Pediatrics; 🇺🇸 Atlanta, Georgia, United States

Indiana Hemophilia and Thrombosis Center; 🇺🇸 Indianapolis, Indiana, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Kentucky Hemophilia Treatment Center; 🇺🇸 Lexington, Kentucky, United States

Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

Rochester General Hospital; 🇺🇸 Rochester, New York, United States

Hemophilia Center of Western PA; 🇺🇸 Pittsburgh, Pennsylvania, United States

Q.E.II Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

University of Texas; 🇺🇸 Houston, Texas, United States

Comprehensive Center for Bleeding Disorders; 🇺🇸 Milwaukee, Wisconsin, United States

Hannover Medical School - Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation; 🇩🇪 Hannover, Germany

Vivantes Klinikum im Friedrichshain; 🇩🇪 Berlin, Germany

Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia; 🇮🇹 Naples, Italy

University of Padua Medical School; 🇮🇹 Padua, Italy

Royal Cornwall Hospital; 🇬🇧 Truro, United Kingdom

Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre; 🇬🇧 Manchester, United Kingdom

Imperial College School of Medicine, Hammersmith Hospital; 🇬🇧 London, United Kingdom

West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom