Hereditary severe von Willebrand Disease in children MedDRA version: 19.0 Level: LLT Classification code 10055168 Term: Von Willebrand's factor deficiency System Organ Class: 100000004850
Conditions
Interventions
Product Name: Recombinant von Willebrand Factor 650IU
Product Code: BAX111
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Vonicog alfa
Current Sponsor code: BA
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet ALL of the following criteria are eligible for this study: 1. Diagnosis of severe VWD (defined as VWF:RCo =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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, 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 or investigational device during the course of this study 15. Subject’s legal representative is a family member or employee of the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. 2.To evaluate the safety of Safety of rVWF. 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
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Hemostatic Efficacy Assessments for surgeries are performed immediately after surgery by operating surgeon and then 24 hours after last perioperative rVWF infusion, Day 7 and Day 14 by the investigator. (See section 11 of protocol for reference);Secondary end point(s): Efficacy 1. Number of treated nonsurgical bleeding episodes with an efficacy rating of ‘excellent’ or ‘good’. 2. Number of infusions, rVWF units, and ADVATE units (if needed), per bleeding episode. 3. For elective surgery: an overall assessment of hemostatic efficacy 24 hours after the last perioperative infusion of rVWF, assessed by the Investigator (hematologist) on a 4-point scale. Safety 1. Incidence and severity of adverse events (AEs) by system organ class (SOC) and preferred term. 2. Incidence of thrombotic events. 3. Incidence of severe hypersensitivity reactions. 4. Development of neutralizing antibodies to VWF and FVIII. 5. Development of total binding antibodies to VWF. 6. Development of antibodies to CHO proteins, murine IgG, and rFurin. Pharmacokinetics 1.Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h), area under the plasma concentration/time curve from time 0 to infinity (AUC0-8), mean residence time (MRT), clearance (CL), incremental recovery (IR), in-vivo recovery (IVR), elimination phase half-life (T1/2), and volume of distribution at steady state (Vss) for VWF:RCo. 2. Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h) for VWF:Ag and VWF:CB. Point estimates per age cohort will be presented. 3. Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h) for FVIII activity. Point estimates per age cohort will be presented. | — |
Countries
Austria, Belgium, Canada, Czech Republic, Finland, France, Germany, Italy, Netherlands, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactSanhita Abrol
Baxalta Innovation GmbH
Outcome results
None listed