Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)

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 (FactorVIII 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 substitutiontherapy with von Willebrand factor concentrate to control bleeding

• Participant, who participates in the treatment for bleeding episodes, has had aminimum of 1 documented bleed (medical history) requiring VWF coagulation factorreplacement 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 pregnancytest
• Participant agrees to employ adequate birth control measures for the duration of thestudy
• 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 acquiredcoagulation disorder other than VWD (eg qualitative and quantitative plateletdisorders 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 seasonalallergic 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, allergicrhinitis/conjunctivitis, non-seasonal asthma) at screening.
• Participant has been diagnosed with significant liver disease as evidenced by any ofthe following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal;hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplainedsplenomegaly, history of esophageal varices).
• Participant has been diagnosed with renal disease, with a serum creatinine level ≥2mg/dL.
• In the judgment of the investigator, the participant has another clinicallysignificant concomitant disease (eg, uncontrolled hypertension) that may poseadditional risks for the participant.
• Participant has been treated with an immunomodulatory drug, excluding topicaltreatment (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 orinvestigational device within 30 days prior to enrollment or is scheduled toparticipate in another clinical study involving an investigational product orinvestigational device during the course of this study.
• Participant has a history of drug or alcohol abuse within the 2 years prior toenrollment.
• Participant has a progressive fatal disease and/or life expectancy of less than 3months.
• Participant is identified by the investigator as being unable or unwilling tocooperate with study procedures.
• Participant suffers from a mental condition rendering him/her unable to understand thenature, scope and possible consequences of the study and/or evidence of anuncooperative attitude.
• Participant is in prison or compulsory detention by regulatory and/or juridical order