Health Condition 1: D688- Other specified coagulation defects
Conditions
Interventions
Intervention1: Single arm with 2 sub-arms (surgery, ITI): PEGylated Recombinant Factor VIII
Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII)
Dosage form: injection, powder, lyo
then
ïâ??· 50Ã?±5 IU/kg/day for a further four weeks
then
ïâ??· 50Ã?±5 IU/kg every second day for a further four weeks
then
ïâ??· 50Ã?±5 IU/kg administered twice a week, adjusted as needed to maintain
a FVIII trough level of 1%, for a further 3 months.
Subjects receiving low dose ITI therapy with 3 x 50 IU/kg weekl
Sponsors
Baxalta Innovations GmbH
Baxalta Bioscience India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1.Subject is (FFP) at any time prior to screening 3. Subject has severe hemophilia A (FVIII Subject is immune competent with a CD4+ count > 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 Additional inclusion criteria for Part B (ITI): 1 Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion 2 Subject has a confirmed positive high titer inhibitor ( > 5.00 BU) or has a positive confirmed low titer inhibitor (� 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with a) poorly controlled bleeding despite increased BAX 855 doses, or b) requires bypassing agents to treat bleeding episodes
Exclusion criteria
Exclusion criteria: 1 Subject has detectable FVIII inhibitory antibodies (ââ?°Â¥0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening 2 S2. Subject has a history of FVIII inhibitory antibodies (ââ?°Â¥ 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 Willebrandââ?¬•s disease) 4 Subject has been previously treated with cryoprecipitate or any type of FVIII concentrate other than ADVATE, BAX 855v or FFP, or was administered ADVATE,BAX 855 or FFP for ââ?°Â¥ 3 Eds at any time prior to screening. 5 Subject has received any kind of blood-transfusion such as PRBC, platelets or plasma prior to screening at any time prior to screening 6 The subjectââ?¬•s weight is 7 Subjectââ?¬•s platelet count is 8 Subject has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80 9 Subject has severe chronic hepatic dysfunction [eg, > 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 ( 1212. 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 Ã?±-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 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. Additional exclusion criteria for Part B (ITI) 1 Spontaneous disappearance of the inhibitor prior to ITI 2 FVIII inhibitor titer ââ?°Â¥ 0.6 BU is not confirmed by a second new blood sample drawn within 2 weeks of study site notification of inhibitor and determined at the central laboratory 3 Inability or unwillingness to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of FVIII inhibitor development Success rate of Immune tolerance induction (ITI)Timepoint: Throughout Part A of the study, approximately 5 years Up to 33 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Additional Outcome Measures for ITI: Primary: The success rate of ITI therapy with BAX 855, success being defined as 1) a persistently negative inhibitor titer 0.6 BU (confirmed by central laboratory with second blood specimen obtained within 2 months); 2) a FVIII IR 66% of baseline value following a wash-out period of 84-96 h, and 3) a FVIII half-life of ââ?°Â¥ 6 hours. Timepoint: If no baseline IR is available, the IR value is indicative of an adequate clinical response following a wash-out period of 84-96 h.;ââ?¬Â¢ Assessment of intra-, post- and perioperative hemostatic efficacy in case of surgery ââ?¬Â¢ Intra- and postoperative blood loss in case of surgery ââ?¬Â¢ IR at baseline and over time ââ?¬Â¢ Half-life at baseline (optional). This is based on an abbreviated PK using 2 post-infusion timepoints: 15-30 minutes and 24ââ?¬â??48 hoursTimepoint: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first) Pre-infusion within 30 minutes; and post-infusion at 15-30 minutes and 24-48 hours;ââ?¬Â¢ABR during ITI ââ?¬Â¢Weight-adjusted consumption of BAX 855 per month and per year for each ITI regimen employed ââ?¬Â¢Catheter-related complications ââ?¬Â¢Binding IgG and IgM antibodies to FVIII, PEG-FVIII, and PEG ââ?¬Â¢The rate of partial success and failure of ITI with BAX 855Timepoint: Up to 33 months;Efficacy ââ?¬Â¢Annualized bleeding rate (ABR) for prophylactic and on-demand treatment ââ?¬Â¢Number of BAX 855 infusions per bleeding episode ââ?¬Â¢Overall hemostatic efficacy rating at 24 h after initiation of treatment and at resolution of bleed ââ?¬Â¢Weight-adjusted consumption of BAX 855 per month, per year and per event (prophylaxis, treatment of bleeding episode and surgery) and the number of infusions per month and per year Timepoint: Throughout Part A of the study, approximately 5 years 24 h after initiation of | — |
Countries
India
Contacts
Public ContactAnoop Singh
Baxalta Bioscience India Pvt. Ltd.
Outcome results
None listed