A preventive study of bleeding episodes for children with severe von Willebrand disease (VWD).
- Conditions
- severe von Willebrand DiseaseMedDRA version: 20.0Level: LLTClassification code 10055168Term: Von Willebrand's factor deficiencySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-003304-13-IT
- Lead Sponsor
- TAKEDA DEVELOPMENT CENTER AMERICAS INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 24
1. The subject has a documented diagnosis of severe VWD (baseline VWF:RCo <20 IU/dL) with a history of substitution therapy with VWF concentrate required to control bleeding and a diagnosis of VWD type 1, type 2 (2A, 2B, 2M, 2N), or type 3.
Diagnosis is confirmed, as applicable, by genetic testing and/or by multimer analysis, which may be documented in patient's history or tested at screening.
2. The subject is <18 years of age at the time of screening.
3. Prescreening treatment requirements:
a. The subject has been receiving On Demand (OD) therapy with VWF products for at least 12 months (for subjects =2 years of age) prior to screening, has experienced at least 1 VWF-treated bleeding event (excluding menorrhagia/heavy menstrual bleeding, as applicable) in the
last 12 months, and prophylactic treatment is recommended by the investigator (Prior OD subjects); or
b. The subject has been receiving prophylactic treatment with plasmaderived (pd)VWF products for at least 12 months prior to screening (for subjects =2 years of age) and switching to prophylaxis with rVWF is recommended by the investigator (Switch subjects),
c. For subjects <2 years of age, the required duration for prior OD therapy with VWF products or for prior prophylactic treatment with pdVWF products is at least 6 months. Prior OD subjects <2 years of age should have experienced at least 1 VWF-treated bleeding event during the last 6 months based on medical records and be recommended to receive prophylactic treatment by the investigator.
4. For subjects =2 years of age, the subject has available records that reliably evaluate type, frequency, severity, and treatment of bleeding episodes for at least 12 months preceding enrollment. For subjects <2 years of age, the subject has available records that reliably evaluate type, frequency, severity and treatment of bleeding episodes for at least 6 months preceding enrollment.
5. If =12 years old at the time of screening, the subject has a body mass index (BMI) =15 but <40 kg/m2. If =2 to <12 years old at the time of screening, the subject has a BMI of =5th and <95th percentile (per Centers for Disease Control and Prevention [CDC] clinical charts). For younger subjects who are <2 years old, the weight-for-age clinical charts (5th to 95th percentile) provided by the CDC should be utilized to ensure the subject has a body weight of =5th and <95th percentiles based on gender (for clinical charts provided by CDC, refer to: https://www.cdc.gov/growthcharts/clinical_charts.htm).
6. Female subjects of childbearing potential (ie, had onset of menses/reached puberty) must have a negative blood/urine pregnancy test result at screening and agree to employ highly effective birth control measures (as defined in the protocol) for the duration of their participation in the study.
7. The subject has voluntarily provided assent (if appropriate) and the legally authorized representative(s) has provided informed consent.
8. The subject and/or legally authorized representative is 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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.
1. The subject has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg, qualitative and quantitative platelet disorders or elevated prothrombin time/international normalized ratio less than 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 an FVIII inhibitor with a titer =0.4 Bethesda units (BU) (by the Nijmegen-modified Bethesda assay) or =0.6 BU (by the 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 less than 200/mm3.
8. The subject has been diagnosed with significant liver disease per the 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 (eg, 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 level =2.5 mg/dL.
10. The subject has a platelet count <100,000/mL at screening (because patients with type 2B VWD are considered eligible for this study, for patients with type 2B VWD, platelet count[s] at screening will be evaluated in consultation with the sponsor, 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 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 not received OD or prophylactic treatment with a VWF product prior to this study.
16. The subject has a progressive fatal disease and/or life expectancy of less than 15 months.
17. The subject is already scheduled for a surgical intervention that will have to be performed while the subject is participating in the study.
18. The subject is unable to complete screening procedures and/or comply with the requirements of the protocol in the opinion of the investigator, based on the joint prescreening evaluation held between the investigator and the sponsor.
19. 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.
20. The subject is member of the study team or in a dependent relationship with one of the study team members, whi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method