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

NCT00816660 | Completed Phase 1 DMC

• 1 other identifier: 070701
• Study Type: interventional
• Target: 32
• Locations: 6 countries
• Sites: 25

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.

Conditions

Von Willebrand Disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

1

EXPERIMENTAL

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

2

ACTIVE COMPARATOR

Biological: Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII); Biological: Marketed plasma-derived VWF/FVIII concentrate

Interventions

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

Single dose, dose escalation, various cohorts

1; 2

Marketed plasma-derived VWF/FVIII concentrate BIOLOGICAL

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

2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (25)

Emory University School of Medicine, Dept. of Pediatrics

Atlanta, Georgia, 30092, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky Hemophilia Treatment Center

Lexington, Kentucky, 40536-0284, United States

Location

Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Brigham & Women´s Hospital, Hematology Division

Boston, Massachusetts, 02115, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, 15213-4306, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, 53225-3548, United States

Location

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

Vienna, 1090, Austria

Location

Q.E.II Health Sciences Centre

Halifax, Nova Scotia, B3H 2YP, Canada

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

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

Hanover, 30625, Germany

Location

Institut für Thrombophilie und Hämostaseologie

Münster, 48143, Germany

Location

Azienda Ospedaliero-universitaria "Careggi"

Florence, 50134, Italy

Location

Giannia Gaslini Children´s Hospital

Genova, 16147, Italy

Location

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

Milan, 20122, Italy

Location

Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia

Naples, 80144, Italy

Location

University of Padua Medical School

Padua, 35128, Italy

Location

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

Vicenza, 80144, Italy

Location

West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital

Birmingham, B15 2TT, United Kingdom

Location

Imperial College School of Medicine, Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre

Manchester, M13 9WL, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23777763 DERIVED

MeSH Terms

Conditions

von Willebrand Diseases

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2009
• First Posted: January 5, 2009
• Study Start: December 1, 2008
• Primary Completion: August 31, 2010
• Study Completion: August 31, 2010
• Last Updated: May 3, 2021

Record last verified: 2021-04

Locations

IT (6); GB (4); AU (1); DE (3); US (10); CA (1)