Severe hemophilia A (FVIII <1%) MedDRA version: 20.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000011915
Conditions
Interventions
Product Name: Pegylated rFVIII
Product Code: BAX 855 250IU/vial
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN:
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Subjects Transitioning from Another BAX 855 study: 1. Subject has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Continuation Study 261302 2. Subject is either receiving on-demand or prophylactic treatment with BAX 855 and had an ABR of = 2 documented and treated during the past 12 months 3. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count = 200 cells/mm3, as confirmed by central laboratory 4. Subject is willing and able to comply with the requirements of the protocol Inclusion Criteria for Newly Recruited Subjects: 1. Subject is 12 to 65 years old at the time of screening 2. Subject has severe hemophilia A (FVIII clotting activity =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Subjects Transitioning from Another BAX 855 study: 1. Subject has developed a confirmed inhibitory antibody to FVIII with a titer of = 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay as determined at the central laboratory during the course of the previous BAX 855 study 2. Subject has been diagnosed with an acquired hemostatic defect other than hemophilia A 3. The subject’s weight is 100 kg 4. Subject’s platelet count is 1.5 times the upper limit of normal) 6. Subject has active hepatic disease with alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) levels = 5 times the upper limit of normal 7. Subject is scheduled to receive systemic immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy during the study 8. Subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject’s safety or compliance 9. Subject is planning to take part in any other clinical study during the course of the study. 10. Subject is 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 Exclusion Criteria for Newly Recruited Subjects 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 confirmed FVIII inhibitors with a titer = 0.6 BU (as determined by the Nijmegen modification of the Bethesda assay or the assay employed with the respective cut-off in the local laboratory) 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. The subject’s weight is 100 kg. 5. Subject’s platelet count is 1.5). 8. Subject has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal) 9. 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 10. Subject is scheduled to receive during the course of the study, a systemic immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a- interferon) othe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare 2 prophylactic dosing regimens of BAX 855 targeting 2 different FVIII trough levels, by comparing the proportions of subjects achieving a total ABR of 0 in the second 6-month study period.; Secondary Objective: To compare the 2 prophylactic dosing regimens of BAX 855 targeting 2 different FVIII trough levels with respect to the following: Proportion of subjects in each prophylactic dosing arm achieving a spontaneous ABR and spontaneous AJBR of 0 in the second 6-m period Proportion of subjects in each prophylactic dosing arm with a total, spontaneous ABR and AJBR <2 Total, spontaneous, and trauma-related ABRs in the 12-m period Reduction in ABR between the two treatment arms and the historical ABR prior to study enrolment Total weight-adjusted consumption of BAX 855 for each prophylactic regimen Joint status using the HJHS and over time HRQoL / Pharmacoeconomic outcomes To determine: hemostatic efficacy of BAX 855 in control of bleeding episodes efficacy of BAX 855 for perioperative management immunogenicity/ safety of BAX 855 PK parameters of BAX 855 at baseline and steady state and the correlation with pre-infusion VWF antigen level IR over time To assess the PROs over time ;Primary end point(s): 1. Presence or absence of any bleedings in the second 6-month study period.; Timepoint(s) of evaluation of this end point: The observation period for the primary endpoint will be the second 6 months of prophylaxis (Day 184 to Day 366). If the subject undergoes a surgical procedure the observation period is interrupted starting from the presurgical loading dose until the subject resumes his previous prophylactic treatment regimen, or until rehabil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy 1. Total, spontaneous and traumatic ABR, and spontaneous AJBR 2. Total weight-adjusted consumption of BAX 855 3. Overall hemostatic efficacy rating at 8 (± 1) hours after the initiation of treatment and at resolution of bleed 4. Number of BAX 855 infusions needed for the treatment of bleeding episodes 5. HJHS 6. Intra-, post- and perioperative hemostatic efficacy in case of surgery 7. Intra- and postoperative blood loss in case of surgery Safety 1. Occurrence of AEs and SAEs 2. Clinically significant changes in vital signs and clinical laboratory parameters (hematology, clinical chemistry, and lipids) 3. Inhibitory antibodies to FVIII, and binding antibodies to FVIII, BAX 855, PEG, and CHO protein Patient Reported Outcomes (PROs) 1. Physical domain and component scores of the SF-36 Health Survey Pharmacokinetics 1. BAX 855 PK parameters based on FVIII activity at baseline and steady state, if applicable: a. AUC0-8 (Area under the plasma concentration versus time curve from time 0 to infinity), IR (incremental recovery) at 15-30 minutes post-infusion, T1/2 (plasma half-life), MRT (mean residence time), CL (clearance), maximum plasma concentration (Cmax) and time to maximum concentration in plasma (Tmax), Vss (Volume of distribution at steady state) b. Incremental recovery (IR) over time ; Timepoint(s) of evaluation of this end point: Individual aspects of the following end points will be evaluated at different time points throughout the study: Efficacy Safety PROs Pharmacokinetics Please refer to the protocol f | — |
Countries
Australia, Austria, Bulgaria, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Malaysia, Poland, Singapore, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactArchana Savla
Baxalta US Inc.
Outcome results
None listed