The primary objective of this study is to assess 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.
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall assessment of hemostatic efficacy assessed by the investigator
(hemophilia physician) 24 hours after last perioperative IP infusion or at
completion of day 14 visit (whichever occurs earlier) will be summarized by the
percentage of subjects in each
efficacy category (*excellent*, *good*, *moderate* and *none*).
Point estimates and corresponding two-sided exact confidence intervals (CIs) at
the 90% confidence level will be calculated for the rate of subjects with an
overall assessment of hemostatic efficacy of *excellent* or *good* 24 hours
after last perioperative IP infusion
or at completion of day 14 visit, whichever occurs earlier.
The primary efficacy analysis will be based on the FAS. As a supportive
analysis, the same calculations will also be carried out on the PPAS.
Secondary outcome
Intraoperative actual versus predicted blood loss as assessed by the operating
surgeon at completion of the surgery will be summarized by the percentage of
subjects in each efficacy category (*excellent*, *good*, *moderate* and *none*).
Point estimates and corresponding two-sided exact confidence intervals (CIs) at
the 90% confidence level will be calculated for the rate of hemostatic efficacy
assessments with excellent/good outcome performed by the operating surgeon
based on the intraoperative
actual versus predicted blood loss.
Intraoperative hemostatic efficacy assessed at completion of surgery by the
operating surgeon will be summarized by the percentage of subjects in each
efficacy category (*excellent*, *good*, *moderate* and *none*).
Point estimates and corresponding two-sided exact confidence intervals (CIs) at
the 90% confidence level will be calculated for the rate of hemostatic efficacy
assessments with excellent/good outcome performed by the operating surgeon at
completion of surgery.
Descriptive statistics (median, quartiles and range) will be used to summarize
the actual blood loss expressed as a percentage of the estimated blood loss
(EBL),
The summary of average daily and total weight-adjusted doses (average through
postoperative day 14) of rVWF with or without ADVATE per subject will be
provided using median, quartiles and range.
The secondary efficacy analysis will be performed on the FAS.
Background summary
Baxter Healthcare Corporation (hereafter referred to as Baxter or sponsor) has
developed a human recombinant von Willebrand Factor (rVWF, BAX 111), which is
synthesized by a genetically engineered Chinese hamster ovary (CHO) cell line
that expresses the von Willebrand factor (VWF) gene. To address concerns
regarding the risk of transmission of blood-borne pathogens that may be
introduced by human plasma, no exogenously added raw materials of human or
animal origin are employed in the cell culture, purification, or formulation of
the final container product. The only proteins present in the final container
product other than rVWF are trace quantities of murine immunoglobulin (IgG,
from the
immunoaffinity purification), host cell (i.e. CHO) protein, rFurin (used to
further process rVWF). This process virtually eliminates any risk of
transmission of human blood-borne viruses or other adventitious agents that
could, in theory, be introduced by the use of added animal- or human-derived
raw materials. rVWF is intended for the treatment of von Willebrand disease
(VWD).
Study objective
The primary objective of this study is to assess 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.
Study design
This is a phase 3 prospective, open-label, uncontrolled, nonrandomized,
international, multicenter study to evaluate the efficacy
and safety of rVWF with or without ADVATE in adults with severe VWD undergoing
major and minor elective surgical procedures.
Intervention
Treatment with rVWF.
Study burden and risks
NA
Industriestrasse 67
Vienna A-1221
AT
Industriestrasse 67
Vienna A-1221
AT
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR 2014-003575-3-NL |
| ClinicalTrials.gov | NCT02283268 |
| CCMO | NL51396.018.14 |