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

This study has been completed.
Sponsor:
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00816660
First received: January 2, 2009
Last updated: November 29, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Von Willebrand Disease
Biological: Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)
Biological: Marketed plasma-derived VWF/FVIII concentrate
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
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)

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • To demonstrate the immediate tolerability and safety after single-dose injections of rVWF:rFVIII at various doses [ Time Frame: Up to 30 days after the last investigational product infusion ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: December 2008
Study Completion Date: October 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)
Single dose, dose escalation, various cohorts
Active Comparator: 2 Biological: Recombinant von Willebrand factor : recombinant FVIII (rVWF:rFVIII)
Single dose, dose escalation, various cohorts
Biological: Marketed plasma-derived VWF/FVIII concentrate
Cross-over: recombinant FVIII (rVWF:rFVIII) and marketed plasma-derived VWF/FVIII concentrate

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00816660

  Show 25 Study Locations
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Tobias Suiter, MD Baxter Healthcare Corporation
  More Information

No publications provided by Baxter Healthcare Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tobias Suiter, MD; Medical Director, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00816660     History of Changes
Other Study ID Numbers: 070701
Study First Received: January 2, 2009
Last Updated: November 29, 2010
Health Authority: United States: Food and Drug Administration
Austria: Federal Ministry for Health Family and Youth
Italy: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Von Willebrand Diseases
Von Willebrand Disease, Type 3
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014