A phase 3 prospective, multicenter study to evaluate efficacy and safety of rVWF with or without ADVATE in elective surgical procedures in subjects with severe von Willebrand disease

Phase 3

Withdrawn

Conditions: extended or excessive bleeding
10035534

Registration Number: NL-OMON42081

Lead Sponsor: Baxalta Innovations GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 2

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Overall assessment of hemostatic efficacy assessed by the investigator<br /><br>(hemophilia physician) 24 hours after last perioperative IP infusion or at<br /><br>completion of day 14 visit (whichever occurs earlier) will be summarized by the<br /><br>percentage of subjects in each<br /><br>efficacy category (excellent, good, moderate and none).<br /><br>Point estimates and corresponding two-sided exact confidence intervals (CIs) at<br /><br>the 90% confidence level will be calculated for the rate of subjects with an<br /><br>overall assessment of hemostatic efficacy of excellent or good 24 hours<br /><br>after last perioperative IP infusion<br /><br>or at completion of day 14 visit, whichever occurs earlier.<br /><br>The primary efficacy analysis will be based on the FAS. As a supportive<br /><br>analysis, the same calculations will also be carried out on the PPAS.</p><br>

Secondary Outcome Measures