Hereditary severe von Willebrand Disease MedDRA version: 19.0 Level: PT Classification code 10047715 Term: Von Willebrand's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 19.0 Level: LLT Classification code 10055168 Term: Von Willebrand's factor deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Recombinant von Willebrand Factor 650IU
Product Code: BAX 111
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: Vonicog alfa
Current Sponsor code:
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. Subject has a documented diagnosis of severe VWD (baseline VWF:RCo =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 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 has received prophylaxis treatment in the 12 months prior to screening (including those who received treatment once a month for menorrhagia but were not treated for any other bleeds). 3. The subject is currently receiving prophylaxis treatment. 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 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 HIV positive with an absolute Helper T cell (CD4) count ?200/mm3. 10. The subject has been diagnosed with significant liver disease 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 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 identified by the investigator as being unable or unwilling to cooperate with study procedures. 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 in prison or compulsory detention by regulatory and/or juridical order 21. 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/conjunctivitis, non-seasonal asthma) the screening visit will be postponed until the subject has recovered.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to prospectively evaluate the annualized bleeding rate (ABR) for spontaneous bleeding episodes while on prophylactic treatment with rVWF and to compare it to the subject’s historical ABR for spontaneous bleeding episodes during on-demand treatment.;Secondary Objective: Secondary Objectives are ? Additional efficacy assessments of prophylactic treatment ? Safety and immunogenicity ? Pharmacokinetics (PK) ? Efficacy of the treatment of bleeding episodes;Primary end point(s): Prospectively recorded ABR for spontaneous (not related to trauma) bleeding episodes during prophylactic treatment with rVWF and the subjects’ historical ABR for spontaneous bleeding episodes during on-demand treatment.;Timepoint(s) of evaluation of this end point: On completion of 12 month prophylactic treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Number (proportion) of subjects with reduction of ABR for spontaneous (not related to trauma) bleeding episodes during prophylaxis relative to the subjects’ own historical ABR during on-demand treatment. Number (proportion) of subjects with 0 bleeds during prophylactic treatment with rVWF. Number of infusions and total weight adjusted consumption of rVWF and ADVATE (recombinant factor VIII/rFVIII) per month and per year during on-demand treatment. Safety Adverse events (AEs) Incidence of thromboembolic events Incidence of severe hypersensitivity reactions Development of neutralizing antibodies to VWF and FVIII Development of total binding antibodies to VWF and FVIII Development of antibodies to Chinese hamster ovary (CHO) proteins, mouse immunoglobulin G (IgG) and rFurin. Pharmacokinetic Incremental recovery (IR), terminal half-life (T1/2), mean residence time (MRT), area under the curve/dose (AUC/dose), area under moment curve/dose (AUMC/dose), volume of distribution at steady state (Vss) and clearance (CL) based on Von Willebrand factor Ristocetin cofactor activity (VWF:RCo), Von Willebrand factor antigen (VWF:Ag), Von Willebrand collagen binding activity (VWF:CB) , INNOVANCE VWF Ac (exploratory assay) and time course (72 hours) of FVIII clotting activity (FVIII:C) levels. Efficacy of the treatment of bleeding episodes Number of infusions of rVWF and ADVATE (rFVIII) per spontaneous bleeding episode. Number of infusions of rVWF and ADVATE (rFVIII) per traumatic bleeding episode. ? Weight-adjusted consumption of rVWF and ADVATE (rFVIII) per spontaneous bleeding episode. Weight-adjusted consumption of rVWF and ADVATE (rFVIII) per traumatic bleeding episode. Overall hemostatic efficacy rating at resolution of bleed;Timepoint(s) of evaluation of this end point: Efficacy parameters evaluated at end of study. Safety parameters evaluated within 24 hrs of awareness. Overall hemostatic efficacy rat | — |
Countries
Canada, Czech Republic, Denmark, Finland, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactSanhita Abrol
Baxalta Innovation GmbH
Outcome results
None listed