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.

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