von Willebrand Disease

The primary objective of the study is to evaluate the hemostatic efficacy and safety of rVWF with or without ADVATE in subjects ( 18 years) diagnosed with hereditary severe VWD undergoing major and minor elective surgical procedures

Recombinant von Willebrand Factor / rVWF (BAX111)

rVWF (BAX111)

injection, powder, lyophilized, for solution/suspension

650

Primary Outcome Measure
Hemostatic efficacy:
Overall assessment of hemostatic efficacy 24 hours after last perioperative IP infusion or at completion of
day 14 visit, whichever occurs earlier, assessed by the investigator (hemophilia physician)

Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1. Diagnosis of severe VWD as listed and elective surgical procedure planned:
 VWD with a history of requiring substitution therapy with von Willebrand factor concentrate
to control bleeding.
 Type 1 (VWF:RCo < 20 IU/dL) or
 Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2N
(Factor VIII coagulation activity [FVIII:C] <10% and historically documented genetics),
Type 2M or
 Type 3 (von Willebrand factor antigen [VWF:Ag] ≤ 3 IU/dL)
2. If type 3 VWD (VWF:Ag ≤ 3 IU/dL), subject has a medical history of at least 20 EDs to VWF/FVIII
coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma).
3. If type 1 or type 2 VWD, subject has a medical history of 5 EDs or a past major surgery requiring
VWF/FVIII coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma).
4. At least 18 years of age
5. If female of childbearing potential, subject presents with a negative pregnancy test
6. If applicable, subject agrees to employ adequate birth control measures for the duration of the study
7. Willing and able to comply with the requirements of the protocol.

Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1. Diagnosis of pseudo VWD or another hereditary or acquired coagulation disorder (eg qualitative and
quantitative platelet disorders or elevated PT/ international normalized ratio [INR]  1.4)
2. History or presence of a VWF inhibitor at screening
3. History or presence of a factor VIII (FVIII) inhibitor with a titer ≥ 0.4 BU (by Nijmegen-modified
Bethesda assay ) or ≥ 0.6 BU (by Bethesda assay)
4. Known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster
proteins
5. Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild
asthma, food allergies or animal allergies
6. Medical history of a thromboembolic event
7. HIV positive with an absolute CD4 count 200/mm3
8. Platelet count < 100,000/mL
9. Diagnosis of significant liver disease, as evidenced by, but not limited to, any of the following: serum
alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein
hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices) or
liver cirrhosis classified as Child B or C
10. Diagnosis of renal disease, with a serum creatinine level ≥2.5 mg/dL
11. Subject has been treated with an immunomodulatory drug, excluding topical treatment (e.g.
ointments, nasal sprays), within 30 days prior to signing the informed consent
12. Subject is pregnant or lactating at the time informed content is obtained.
13. Subject has participated in another clinical study involving an investigational product (IP), other than
rVWF with or without ADVATE , or investigational device within 30 days prior to enrollment or is
scheduled to participate in another clinical study involving an IP or investigational device during the
course of this study. (Eligible patients participating in the rVWF Prophy study [071301] may be
enrolled).
14. Progressive fatal disease and/or life expectancy of less than 3 months
15. Subject is identified by the investigator as being unable or unwilling to cooperate with study
procedures
16. 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
17. Subject is in prison or compulsory detention by regulatory and/or juridical order
18. Member of the study team conducting this study or in a dependent relationship with one of the study
team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings,
parents) as well as employees.