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

NCT ID: NCT00816660

Last Updated: 2021-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-01

Study Completion Date

2010-08-31

Brief Summary

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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

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Conditions

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Von Willebrand Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants

Study Groups

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1

Group Type EXPERIMENTAL

Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)

Intervention Type BIOLOGICAL

Single dose, dose escalation, various cohorts

2

Group Type ACTIVE_COMPARATOR

Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)

Intervention Type BIOLOGICAL

Single dose, dose escalation, various cohorts

Marketed plasma-derived VWF/FVIII concentrate

Intervention Type BIOLOGICAL

Cross-over: recombinant FVIII (rVWF:rFVIII) and marketed plasma-derived VWF/FVIII concentrate

Interventions

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Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)

Single dose, dose escalation, various cohorts

Intervention Type BIOLOGICAL

Marketed plasma-derived VWF/FVIII concentrate

Cross-over: recombinant FVIII (rVWF:rFVIII) and marketed plasma-derived VWF/FVIII concentrate

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baxalta now part of Shire

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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Emory University School of Medicine, Dept. of Pediatrics

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

Site Status

University of Kentucky Hemophilia Treatment Center

Lexington, Kentucky, United States

Site Status

Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Brigham & Women´s Hospital, Hematology Division

Boston, Massachusetts, United States

Site Status

Rochester General Hospital

Rochester, New York, United States

Site Status

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas

Houston, Texas, United States

Site Status

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, United States

Site Status

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

Vienna, , Austria

Site Status

Q.E.II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Site Status

Hannover Medical School - Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation

Hanover, , Germany

Site Status

Institut für Thrombophilie und Hämostaseologie

Münster, , Germany

Site Status

Azienda Ospedaliero-universitaria "Careggi"

Florence, , Italy

Site Status

Giannia Gaslini Children´s Hospital

Genova, , Italy

Site Status

Ospedale Maggiore di Milano, Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"

Milan, , Italy

Site Status

Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia

Naples, , Italy

Site Status

University of Padua Medical School

Padua, , Italy

Site Status

Ospedale di Vicenza - U.L.S.S.N.6

Vicenza, , Italy

Site Status

West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Imperial College School of Medicine, Hammersmith Hospital

London, , United Kingdom

Site Status

Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre

Manchester, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Countries

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United States Austria Canada Germany Italy United Kingdom

References

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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.

Reference Type DERIVED
PMID: 23777763 (View on PubMed)

Other Identifiers

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070701

Identifier Type: -

Identifier Source: org_study_id

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