A study to determine the effectiveness, safety, and tolerability of the Recombinant Von Willebrand Factor administered with or without Advate for children diagnosed with Severe von Willebrand Disease who experience bleeding episodes and/or will undergo major, minor or oral surgery procedures.
- Conditions
- Hereditary severe von Willebrand Disease in childrenTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-001477-33-Outside-EU/EEA
- Lead Sponsor
- Baxalta Innovations GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- Not specified
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 studyii
6. Subject and/or legally authorized representative are willing and able to comply with the requirements of the protocol, which should also be confirmed based on a pre-screening
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 both previously treated subjects as well as for subjects undergoing surgery are as follows:
1. Unable to tolerate or are inadequately responsive to deamino-delta-D-arginine vasopressin (DDAVP)
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 VWF replacement therapy
Additional inclusion criterion for previously untreated subjects are as follows:
1. The subject has not received prior VWF coagulation factor replacement therapy
Are the trial subjects under 18? yes
Number of subjects for this age range: 34
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.1.3.1 Number of subjects for this age range
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 [PT]/international normalized ratio [INR] >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 (HIV) 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 (ALT) of 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, a-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 other than rVWF 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the hemostatic efficacy and safety of rVWF, with or without ADVATE, in the treatment and control of nonsurgical bleeding events in pediatric subjects (<18 years of age) diagnosed with severe, hereditary VWD.;Secondary Objective: 1. Elective or emergency surgery:to evaluate the of hemostatic efficacy after the last perioperative rVWF infusion.<br>2. To evaluate the safety of Safety of rVWF.<br>3. To evaluate the PK parameters of rVWF.;Primary end point(s): The primary outcome measure is hemostatic efficacy, defined as the number of pediatric subjects with treatment success for rVWF-treated nonsurgical bleeding episodes (using a 4-point scale). Bleeding episode treatment success is defined as a mean efficacy rating score of <2.5.;Timepoint(s) of evaluation of this end point: Timepoint of assessment is within 24 hrs after onset of each bleeding episode an infusion of study drug, recording is made after resolution of each bleeding episode.
- Secondary Outcome Measures
Name Time Method