A Phase 3, Prospective, Multicenter, Uncontrolled, Open-Label Clinical Study to Determine the Efficacy, Safety, and Tolerability of rVWF with or without ADVATE in the Treatment and Control of Bleeding Episodes, the Efficacy and Safety of rVWF in Elective and Emergency Surgeries, and the Pharmacokinetics (PK) of rVWF in Children Diagnosed with Severe von Willebrand Disease
- Conditions
- bleeding disorderHemophilia10018849
- Registration Number
- NL-OMON50545
- Lead Sponsor
- Baxalta Inovation GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 1
Subjects who meet ALL of the following criteria are eligible for this
study:
1. Diagnosis of severe VWD (defined as VWF:RCo <20%):
a. Type 1 (VWF:RCo <20 IU/dL); or
b. Type 2A (VWF:RCo <20 IU/dL), Type 2B (as diagnosed by genotype),
Type 2N (FVIII:C
<10% and historically documented genetics), Type 2M; or
c. Type 3 (VWF:Ag *3 IU/dL).
2. Age 0 to <18 years at the time of screening
3. The subject has provided assent (if appropriate) and legally
authorized representative(s) has
provided informed consent
4. If female of childbearing potential, subject presents with a negative
serum pregnancy test
5. If applicable, subject agrees to employ adequate birth control
measures for the duration of the study
6. Subject and/or the legally authorized representative are willing and able to
comply with the requirements of the protocol, which should also be confirmed
based on a prescreening evaluation held between the Investigator and the
Sponsor, to ensure no eminent risk is present that could challenge the
subject's compliance with the study requirements.
Additional inclusion criteria for previously treated subjects and subjects
undergoing surgery are as follows:
1. Unable to tolerate or are inadequately responsive to deamino-delta-Darginine
vasopressin
2. The subject has had a minimum of 1 documented bleed requiring VWF
coagulation factor
replacement therapy (ie, treatment with a VWF product) during the previous 12
months prior to enrollment
and overall historically
3 or more exposure days (EDs) to plasma-derived VWF.
Additional inclusion criterion for previously untreated subjects are as
follows:
1. The subject has not received prior VWF coagulation factor
replacement therapy
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 prothrombin
time/international normalized ratio
>1.4)
2. History or presence of a VWF inhibitor at Screening
3. History or presence of a FVIII inhibitor with a titer *0.4 Bethesda
units (BU) (by Nijmegen assay)
or *0.6 BU (by Bethesda assay)
4. Documented history of a VWF:RCo half-life <6 hours
5. Known hypersensitivity to any of the components of the study drug,
such as mouse or hamster
proteins
6. Medical history of immunological disorders, excluding seasonal
allergic rhinitis/ conjunctivitis/
asthma, food allergies, or animal allergies
7. Medical history of a thromboembolic event
8. Human immunodeficiency virus positive, with an absolute CD4 count
*200/mm3
9. In the judgment of the Investigator, the subject has another clinically
significant concomitant
disease (eg, uncontrolled hypertension, cancer) that may pose additional
risks for the subject
10. Diagnosis of significant liver disease, as evidenced by, but not
limited to, any of the following:
serum alanine aminotransferase 5 times the upper limit of normal;
hypoalbuminemia; portal vein
hypertension (eg, presence of otherwise unexplained splenomegaly,
history of esophageal varices)
or liver cirrhosis classified as Child B or C
11. Diagnosis of renal disease, with a serum creatinine level *2.5 mg/dL
12. Immunomodulatory drug treatment other than anti-retroviral
chemotherapy (eg, *-interferon, or
corticosteroid agents at a dose equivalent to hydrocortisone greater than
10 mg/day (excluding
topical treatment [eg, ointments, nasal sprays]), within 30 days prior to
signing the informed
consent (or assent, if appropriate)
13. If female, subject is pregnant or lactating at the time informed
consent (or assent, if appropriate) is
obtained
14. Subject has participated in another clinical study involving an 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
15. Subject's legal representative is a family member or employee of the
Investigator
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary outcome measure is hemostatic efficacy, defined as the number of<br /><br>pediatric subjects with treatment success for rVWF-treated<br /><br>nonsurgical bleeding episodes (using a 4-point scale). Bleeding episode<br /><br>treatment success is defined as a mean efficacy rating score of <2.5.<br /><br><br /><br>Timepoint of evaluation:<br /><br>Timepoint of assessment is within 24 hrs after onset of each bleeding episode<br /><br>an infusion of study drug, recording is made after resolution of each bleeding<br /><br>episode.</p><br>
- Secondary Outcome Measures
Name Time Method