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

April 29, 2021 updated by: Baxalta now part of Shire

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien), University Department for Internal Medicine I
  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2YP
        • Q.E.II Health Sciences Centre
  • Germany
      • Berlin, Germany, 10249
        • Vivantes Klinikum im Friedrichshain
      • Hannover, Germany, 30625
        • Hannover Medical School - Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation
      • Münster, Germany, 48143
        • Institut für Thrombophilie und Hämostaseologie
  • Italy
      • Firenze, Italy, 50134
        • Azienda Ospedaliero-universitaria "Careggi"
      • Genova, Italy, 16147
        • Giannia Gaslini Children´s Hospital
      • Milan, Italy, 20122
        • Ospedale Maggiore di Milano, Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"
      • Naples, Italy, 80144
        • Ospedale San Giovanni Bosco, Centro Emofilia Divisione di Ematologia
      • Padua, Italy, 35128
        • University of Padua Medical School
      • Vicenza, Italy, 80144
        • Ospedale di Vicenza - U.L.S.S.N.6
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TT
        • West Midlands Region Adult Haemophilia Centre, Queen Elizabeth Hospital
      • London, United Kingdom, W12 0NN
        • Imperial College School of Medicine, Hammersmith Hospital
      • Manchester, United Kingdom, M13 9WL
        • Central Manchester Healthcare NHS Trust, Manchester Haemophilia Comprehensive Care Centre
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30092
        • Emory University School of Medicine, Dept. of Pediatrics
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Indiana Hemophilia and Thrombosis Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0284
        • University of Kentucky Hemophilia Treatment Center
      • Louisville, Kentucky, United States, 40202
        • Brown Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women´s Hospital, Hematology Division
    • New York
      • Rochester, New York, United States, 14621
        • Rochester General Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213-4306
        • Hemophilia Center of Western PA
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53225-3548
        • Comprehensive Center for Bleeding Disorders

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Up to 30 days after the last investigational product infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baxalta now part of Shire

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2008

Primary Completion (Actual)

August 31, 2010

Study Completion (Actual)

August 31, 2010

Study Registration Dates

First Submitted

January 2, 2009

First Submitted That Met QC Criteria

January 2, 2009

First Posted (Estimate)

January 5, 2009

Study Record Updates

Last Update Posted (Actual)

May 3, 2021

Last Update Submitted That Met QC Criteria

April 29, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 070701

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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