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

Von Willebrand Disease Clinical Trial

Official title:

Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex (rVWF:rFVIII): A Phase 1 Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability in Type 3 Von Willebrand Disease (VWD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00816660
• Other study ID #: 070701
• Status: Completed
• Phase: Phase 1
• Start date: December 1, 2008
• Est. completion date: August 31, 2010

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 31, 2010
• Est. primary completion date: August 31, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Von Willebrand Disease
• Von Willebrand Diseases

Intervention

Biological:
• Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)
Single dose, dose escalation, various cohorts
• Marketed plasma-derived VWF/FVIII concentrate
Cross-over: recombinant FVIII (rVWF:rFVIII) and marketed plasma-derived VWF/FVIII concentrate

Locations

Country	Name	City	State
Austria	General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien), University Department for Internal Medicine I	Vienna
Canada	Q.E.II Health Sciences Centre	Halifax	Nova Scotia
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Hannover Medical School - Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation	Hannover
Germany	Institut für Thrombophilie und Hämostaseologie	Münster
Italy	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	Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia	Naples
Italy	University of Padua Medical School	Padua
Italy	Ospedale di Vicenza - U.L.S.S.N.6	Vicenza
United Kingdom	West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital	Birmingham
United Kingdom	Imperial College School of Medicine, Hammersmith Hospital	London
United Kingdom	Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre	Manchester
United Kingdom	Royal Cornwall Hospital	Truro
United States	Emory University School of Medicine, Dept. of Pediatrics	Atlanta	Georgia
United States	Brigham & Women´s Hospital, Hematology Division	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Texas	Houston	Texas
United States	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana
United States	University of Kentucky Hemophilia Treatment Center	Lexington	Kentucky
United States	Brown Cancer Center	Louisville	Kentucky
United States	Comprehensive Center for Bleeding Disorders	Milwaukee	Wisconsin
United States	Hemophilia Center of Western PA	Pittsburgh	Pennsylvania
United States	Rochester General Hospital	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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