Clinical trial NCT00816660: Pharmacokinetic, Safety and Tolerability Study of Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex in Type 3 Von Willebrand Disease
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Von Willebrand Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-01-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: To demonstrate the immediate tolerability and safety after single-dose injections of rVWF:rFVIII at various doses
timeFrame: Up to 30 days after the last investigational product infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine, Dept. of Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Hemophilia Treatment Center
state: Kentucky
city: Louisville
country: United States
facility: Brown Cancer Center
state: Kentucky
city: Boston
country: United States
facility: Brigham & Women´s Hospital, Hematology Division
state: Massachusetts
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Milwaukee
country: United States
facility: Comprehensive Center for Bleeding Disorders
state: Wisconsin
city: Vienna
country: Austria
facility: General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien), University Department for Internal Medicine I
city: Halifax
country: Canada
facility: Q.E.II Health Sciences Centre
state: Nova Scotia
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Hannover
country: Germany
facility: Hannover Medical School - Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation
city: Münster
country: Germany
facility: Institut für Thrombophilie und Hämostaseologie
city: Firenze
country: Italy
facility: Azienda Ospedaliero-universitaria "Careggi"
city: Genova
country: Italy
facility: Giannia Gaslini Children´s Hospital
city: Milan
country: Italy
facility: Ospedale Maggiore di Milano, Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"
city: Naples
country: Italy
facility: Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia
city: Padua
country: Italy
facility: University of Padua Medical School
city: Vicenza
country: Italy
facility: Ospedale di Vicenza - U.L.S.S.N.6
city: Birmingham
country: United Kingdom
facility: West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Imperial College School of Medicine, Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Mannucci PM, Kempton C, Millar C, Romond E, Shapiro A, Birschmann I, Ragni MV, Gill JC, Yee TT, Klamroth R, Wong WY, Chapman M, Engl W, Turecek PL, Suiter TM, Ewenstein BM; rVWF Ad Hoc Study Group. Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial. Blood. 2013 Aug 1;122(5):648-57. doi: 10.1182/blood-2013-01-479527. Epub 2013 Jun 18.