A prospective, phase 3, open label, international multicenter study on efficacy and safety of prophylaxis with rVWF in severe von willebrand disease
- Conditions
- Inherited severe bleeding disorderVon Willebrand's10005330
- Registration Number
- NL-OMON47063
- Lead Sponsor
- Baxalta Innovations GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 1
Subjects who meet ALL of the following criteria are eligible for this study:
1. Subject has a documented diagnosis of severe VWD (baseline VWF:RCo <20 IU/dL) with a history of requiring substitution therapy with von Willebrand factor concentrate
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).
2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening.
3. For on-demand patient groep, subject currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator.
4. For pdVWF switch patient group, subject has been receiving prophylactic treatment of pdVWF products for no less than 12 months prior to screening.
5. For on-demand patient groep, subject has >=3 documented spontaneous bleeds (ont including menorrhagia) requiring VWF treatment during the past 12 months.
6. Availability of records to reliably evaluate type, frequency and treatment of bleeding episodes during at least 12 months preceeding enrollment.
Up to 24 months of retrospective data should be collected if available. Availability of dosing and factor consumption during 12 months (up to 24 months) of treatment prior to enrollment is required for pdVWF switch subjects and is desired (but not a requirement) for on-demand subjects.
7. Subject is >=18 years old at the time of screening and has a body mass index >=15 but <40 kg/m2.
8. If female of childbearing potential, subject presents with a negative blood/urine pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study.
9. Subject is willing and able to comply with the requirements of the protocol.
Subjects who meet ANY of the following criteria are not eligible for this study:
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 (PT)/international normalized ratio [INR] 1.4).
2. The subject is currently receiving prophylaxis treatment with more than 5 infusions per week.
3. The subject is currently receiving prophylaxis treatment with a weekly dose exceeding 240 IU/kg.
4. The subject has a history or presence of a VWF inhibitor at screening.
5. 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).
6. The subject has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.
7. The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
8. The subject has a medical history of a thromboembolic event.
9. The subject is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count 200/mm3.
10. 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 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).
11. The subject has been diagnosed with renal disease, with a serum creatinine (CR) level >=2.5 mg/dL.
12. The subject has a platelet count <100,000/mL at screening.
13. The 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.
14. The subject is pregnant or lactating at the time of enrollment.
15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
16. 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.
17. The subject has a progressive fatal disease and/or life expectancy of less than 15 months.
18. The subject is scheduled for a surgical intervention.
19. The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
20. 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.
21. The subject is in prison or compulsory detention by regulatory and/or juridical order
22. 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 employees.
Delay criteria
1. If the subject presents with an acute bleeding episodes or acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Annualized bleeding rate (ABR) for spontaneous (not related to trauma) bleeding<br /><br>episodes during prophylactic treatment with rVWF (vonicog alfa).</p><br>
- Secondary Outcome Measures
Name Time Method