Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)
Condition: Von Willebrand Disease
MeSH terms: Von Willebrand Diseases
Intervention: Recombinant von Willebrand factor (rVWF); Placebo; Recombinant factor VIIII (rFVIII)
Intervention description: Intravenous administration; Syringe supplied with physiologic saline solution for infusion; Intravenous administration
Intervention MeSH terms: Factor VIII
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this Phase 3 study is to assess the pharmacokinetics of rVWF:rFVIII and rVWF,
      and to assess the safety and efficacy of rVWF:rFVIII and rVWF in the treatment of bleeding
      events in subjects with severe hereditary von Willebrand disease (VWD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant has been diagnosed with:

               1. Type 1 (Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) < 20 IU/dL)
                  or,

               2. Type 2A (VWF:RCo < 20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor
                  VIII activity (FVIII:C) <10% and historically documented genetics), Type 2M or,

               3. Type 3 ( Von Willebrand factor antigen (VWF:Ag) ≤ 3 IU/dL) or,

               4. Severe Von Willebrand disease (VWD) with a history of requiring substitution
                  therapy with von Willebrand factor concentrate to control bleeding

          -  Participant, who participates in the treatment for bleeding episodes, has had a
             minimum of 1 documented bleed (medical history) requiring VWF coagulation factor
             replacement therapy during the previous 12 months prior to enrollment.

          -  Participant has a Karnofsky score ≥ 60%

          -  Participant is at least 18 and not older than 65 years of age at enrollment

          -  If female of childbearing potential, participant presents with a negative pregnancy
             test

          -  Participant agrees to employ adequate birth control measures for the duration of the
             study

          -  Participant is willing and able to comply with the requirements of the protocol

        Exclusion Criteria:

          -  Participant has been diagnosed with pseudo VWD or another hereditary or acquired
             coagulation disorder other than VWD (eg qualitative and quantitative platelet
             disorders or elevated PT/international normalized ratio [INR] >1.4).

          -  Participant has a documented history of a VWF:RCo half-life of <6 hours.

          -  Participant has a history or presence of a VWF inhibitor at screening.

          -  Participant has a history or presence of a factor VIII (FVIII) inhibitor with a titer
             ≥0.4 BU (by Nijmegen assay) or ≥ 0.6 BU (by Bethesda assay).

          -  Participant has a known hypersensitivity to any of the components of the study drugs,
             such as mouse or hamster proteins.

          -  Participant has a medical history of immunological disorders, excluding seasonal
             allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.

          -  Participant has a medical history of a thromboembolic event.

          -  Participant is HIV positive with an absolute CD4 count <200/mm3.

          -  Participant has been diagnosed with cardiovascular disease (New York Heart Association
             [NYHA] classes 1-4.

          -  Participant has an acute illness (eg, influenza, flu-like syndrome, allergic
             rhinitis/conjunctivitis, non-seasonal asthma) at screening.

          -  Participant has been diagnosed with significant liver disease as evidenced by any of
             the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal;
             hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained
             splenomegaly, history of esophageal varices).

          -  Participant has been diagnosed with renal disease, with a serum creatinine level ≥2
             mg/dL.

          -  In the judgment of the investigator, the participant has another clinically
             significant concomitant disease (eg, uncontrolled hypertension) that may pose
             additional risks for the participant.

          -  Participant has been treated with an immunomodulatory drug, excluding topical
             treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment

          -  Participant is pregnant or lactating at the time of enrollment.

          -  Participant has participated in another clinical study involving an IP or
             investigational device within 30 days prior to enrollment or is scheduled to
             participate in another clinical study involving an investigational product or
             investigational device during the course of this study.

          -  Participant has a history of drug or alcohol abuse within the 2 years prior to
             enrollment.

          -  Participant has a progressive fatal disease and/or life expectancy of less than 3
             months.

          -  Participant is identified by the investigator as being unable or unwilling to
             cooperate with study procedures.

          -  Participant 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.

          -  Participant is in prison or compulsory detention by regulatory and/or juridical order