Severe hemophilia A (FVIII <1%) MedDRA version: 20.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
Conditions
Interventions
Product Name: PEGylated rFVIII
Product Code: BAX855
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: Not applicable
Current Sponsor code: BAX855
Other descripti
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is 200 cells/mm3, as confirmed by central laboratory at screening 5. Parent or legally authorized representative is willing and able to comply with the requirements of the protocol Are the trial subjects under 18? yes Number of subjects for this age range: 120 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
Exclusion criteria
Exclusion criteria: 1. Subject has detectable FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening 2. Subject has a history of FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening 3. Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease) 4. Subject has been previously treated with cryoprecipitate or any type of FVIII concentrate other than ADVATE or BAX 855, or was administered ADVATE or BAX 855 or plasma transfusion for = 3 EDs at any time prior to screening 5. Subject receives > 2 EDs of ADVATE in total during the periods prior to enrollment and during the screening period, up until the baseline infusion. 6. The subject’s weight is anticipated to be 5 times upper limit of normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or a documented INR > 1.5] in his medical history or at the time of screening 10. Subject has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal) 11. Subject has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation 12. Subject is scheduled to receive during the course of the study a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy 13. Subject has participated in another clinical study involving an 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 14. Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance 15. Parent, legally authorized representative or subject are a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine safety including immunogenicity of BAX 855 based on the incidence of inhibitor development to FVIII (= 0.6 Bethesda unit/mL using the Nijmegen modification of the Bethesda assay);Secondary Objective: Safety 1. To determine the immunogenicity of BAX 855 in terms of binding IgG and IGM antibodies to FVIII, PEG-FVIII and PEG 2. To determine the safety of BAX 855 based on adverse events (AEs) and serious adverse events (SAEs) Hemostatic Efficacy 3. To assess the efficacy of prophylactic treatment with BAX 855 4. To characterize the efficacy of BAX 855 in the control of bleeding episodes Pharmacokinetics 6. To determine the incremental recovery (IR) of BAX 855 at baseline and over time 7. To determine half-life of BAX 855 at baseline (optional);Primary end point(s): Incidence of FVIII inhibitor development The success rate of ITI therapy with BAX 855;Timepoint(s) of evaluation of this end point: The set of subjects to be analyzed includes all subjects who developed a confirmed inhibitor (at any time) based on a second repeat blood sample within 2 weeks of sitenotification of an inhibitor and all subjects who did not develop an inhibitor and had = 100 EDs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Binding IgG and IgM antibodies to FVIII, PEG-FVIII and PEG AEs and SAEs Clinically significant changes in vital signs and clinical laboratory parameters (hematology and clinical chemistry) Efficacy: -Annualized bleeding rate (ABR) for prophylactic and on-demand treatment -Number of BAX 855 infusions per bleeding episode -Overall hemostatic efficacy rating at 24 h after initiation of treatment and at resolution of bleed -Weight-adjusted consumption of BAX 855 per month, per year and per event (prophylaxis and treatment of bleeding episode) and the number of infusions per month and per year Pharmacokinetics: -IR at baseline and over time -Half-life at baseline (optional);Timepoint(s) of evaluation of this end point: Binding antibodies to FVIII, BAX 855 and PEG and all other secondary safety outcome measures will be analyzed descriptively. The ABR will be analyzed by point and interval estimates derived from a negative binomial model with treatment regimen (on-demand vs. prophylaxis) as a covariate and the duration of the observation period as an offset. Other secondary efficacy outcome measures as well as IR over time will be analyzed descriptively. | — |
Countries
Austria, Belgium, Bulgaria, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Hungary, India, Italy, Korea, Republic of, Malaysia, Netherlands, Norway, Poland, Romania, Singapore, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactArchana Savla
Baxalta US Inc
Outcome results
None listed