A phase 3b, prospective, open-label, uncontrolled, multicenter study on long-term safety and efficacy of rVWF in pediatric and adult subjects with severe von Willebrand disease (VWD)
- Conditions
- Hemophilia10018849bleeding disorder
- Registration Number
- NL-OMON52575
- Lead Sponsor
- Baxalta Innovation GmbH - part of Shire
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
Subjects who have completed Study 071301 or 071102 (or subjects who have
completed the surgery in Study 071102 and want to continue to receive OD
treatment) and are willing to immediately transition into this study, must
meet the following 2 criteria to be eligible for this study:
1. If female of childbearing potential, has a negative blood/urine pregnancy
test at screening and agrees to employ
highly effective birth control measures (including sterilization, implant,
intra-uterine device (IUD), correct and consistent use of hormonal
contraception, and abstinence) for the duration of the study.
2. Subject and/or legally authorized representative is willing and able to
comply with the requirements of the protocol.
New subjects (Cohort 4) who meet the above 2 and ALL the following additional
criteria are eligible for this study:
3. Subject has a documented diagnosis of severe VWD (baseline VWF:RCo <20
IU/dL) with a history of requiring substitution therapy with rVWF concentrate
required to control bleeding:
a. Type 1 (VWF:RCo <20 IU/dL) or,
b. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by
genotype), Type 2M or,
c. Type 3 (VWF:Ag <=3 IU/dL).
Diagnosis is confirmed by genetic testing and multimer analysis, documented in
patient history or at screening.
4. Subject has been receiving OD therapy with VWF products for at least 12
months, and prophylactic treatment
is recommended by the investigator.
5. Subject has >=3 documented spontaneous bleeds (not including menorrhagia)
requiring VWF treatment during the past 12 months.
6. Subject has available records that reliably evaluate type, frequency, and
treatment of bleeding episodes for at least 12 months preceding enrollment; up
to 24 months of retrospective data should be collected if available.
7. Subject is >=12 years old at the time of screening and has a body mass index
>=15 but <40 kg/m2.
The subject will be excluded from the study if any of the following exclusion
criteria are met:
1. The subject has been diagnosed with Type 2N VWD, pseudo VWD, or another
hereditary or acquired coagulation disorder other than VWD (e.g, qualitative
and quantitative platelet disorders or elevated prothrombin time/international
normalized ratio >1.4).
2. The subject has a history or presence of a VWF inhibitor at screening.
3. The subject has a history or presence of a FVIII inhibitor with a titer >=0.4
Bethesda units (BU) (by Nijmegen modified Bethesda assay) or >=0.6 BU (by
Bethesda assay).
4. The subject has a known hypersensitivity to any of the components of the
study drugs, such as mouse or hamster proteins.
5. The subject has a medical history of immunological disorders, excluding
seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or
animal allergies.
6. The subject has a medical history of a thromboembolic event.
7. The subject is human immunodeficiency virus (HIV) positive with an absolute
Helper T cell (CD4) count <200/mm3.
8. The subject has been diagnosed with significant liver disease per
investigator*s medical assessment of the subject*s current condition or medical
history or as evidenced by, but not limited to any of the following:
serum alanine aminotransferase (ALT) greater than 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-Pugh class B or C.
9. The subject has been diagnosed with renal disease, with a serum creatinine
(CR) level >=2.5 mg/dL.
10. The subject has a platelet count <100,000/mL at screening. (for subjects
with type 2B VWD, platelet count(s) at screening will be evaluated taking into
consideration historical trends in platelet counts and the Investigator's
medical assessment of the patient's condition).
11. The subject has been treated with an immunomodulatory drug, excluding
topical treatment (eg, ointments, nasal sprays), within 30 days prior to
signing the informed consent (or assent, if appropriate).
12. The subject is pregnant or lactating at the time of enrollment.
13. The subject has cervical or uterine conditions causing menorrhagia or
metrorrhagia (including infection, dysplasia).
14. The subject has participated in another clinical study involving another
investigational product (IP) 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.
15. The subject has a progressive fatal disease and/or life expectancy of less
than 15 months.
16. For new OD subjects, the subject is scheduled for a surgical intervention.
17. The subject is identified by the investigator as being unable or unwilling
to cooperate with study procedures.
18. The subject has 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.
19. The subject is member of the study team or in a dependent relationship with
one of the study team members which includes close relatives (i.e., children,
partner/spouse, siblings, and parents) as well as emplo
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Spontaneous ABR during prophylaxis treatment with rVWF (vonicog alfa) based on<br /><br>the data collected during the first 12 months on study treatment.</p><br>
- Secondary Outcome Measures
Name Time Method