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

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