pharmacokinetic, safety and tolerability study of recombinant von willebrand factor / recombinant factor viii complex in type 3 von willebrand disease

Conditions: Von Willebrand Disease

Summary: 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.


Eligibility criteria:
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