Severe hemophilia A (FVIII<1%) MedDRA version: 19.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
Conditions
Interventions
Product Name: PEGylated rFVVIII
Product Code: BAX 855
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: not applicable
Current Sponsor code: BAX 855
Other d
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Subject requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy). 2. Subject and/or legal representative has/have provided signed informed consent. 3. Subject is 2 to 75 years of age at the time of enrollment. 4. Subject is male with severe hemophilia A (FVIII level =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Subject has detectable FVIII inhibitory antibodies (=0.4 BU using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (=0.4 BU using the Nijmegen modification of the Bethesda assay or =0.6 BU using the Bethesda assay). 2. History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC). 3. Subject has a platelet count 2.0 mg/dL), as confirmed by central laboratory at screening. 5. Subject has severe chronic hepatic dysfunction (eg =5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented INR > 1.5). 6. Subject has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG. 7. Subject is currently using or has recently (< 30 days) used pegylated drugs (other than BAX855) prior to study participation or is scheduled to use such drugs during trial participation. 8. Subject is currently participating in another clinical drug (other than BAX855) or device study or use of another investigational product or device within 30 days prior to study entry. 9. Subject has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A. 10. Subject is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (e.g., systemic corticosteroid agent at a dose equivalent to hydrocortisone greater than 10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy. 11. 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 safety or compliance. 12. the subject has an incremental recovery <1.5 IU/dL:IU/kg as determined in the parent study if applicable 13. Subjects undergoing minor or major emergency surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the peri-operative hemostatic efficacy of BAX855 in male PTPs aged 2 - 75 years with severe hemophilia A (FVIII <1%) undergoing major or minor, elective or minor emergency surgical, dental or other invasive procedures.;Secondary Objective: To determine the safety of BAX855 used in the perioperative setting o The occurrence of all AEs o The occurrence of thrombotic events and/or allergic reactions to BAX855 o To determine the development of FVIII inhibitors and binding antibodies to FVIII, BAX855 and PEG, as well as antibodies to Chinese Hamster Ovary (CHO) proteins • To determine the intra-and postoperative blood loss at the end of surgery and until drain removal, if applicable, compared to the estimated volume of expected average and maximum blood loss in a comparable healthy individual as predicted preoperatively by the investigator/surgeon To determine the volume of blood, red blood cells, platelets, and other blood products transfused • To determine the daily and total weight-adjusted consumption of BAX855 per subject;Primary end point(s): Global Hemostatic Efficacy score, which is composed of 3 individual ratings: 1. Assessment of intra-operative hemostatic efficacy of BAX855 performed by the operating surgeon 2. Assessment of postoperative hemostatic efficacy of BAX855 at postoperative day 1 performed by the operating surgeon 3. Assessment of postoperative hemostatic efficacy of BAX855 at EOS visit performed by the investigator (day 14 or discharge, whichever is first);Timepoint(s) of evaluation of this end point: 6 months (±2 weeks) for first and secondary endpoints | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SAFETY • Development of neutralizing FVIII inhibitors • Development of binding antibodies to FVIII, BAX855, and PEG • Development of anti-CHO antibodies. • Occurrence of thrombotic events • Other IP-related adverse events (AEs) • Clinically significant changes in vital signs and routine laboratory parameters (hematology, clinical chemistry and virology) Pharmacokinetics of BAX855 Primary PK:IR and T1/2. Secondary PK: AUC0-8/dose (area under the plasma concentration /time curve from time 0 to infinity), MRT, CL, Vss, AUC0-96h/dose (area under the plasma concentration/time curve from time 0 to 96 hours post-infusion. Blood loss The observed versus predicted operative blood loss will be described for the period from initiation of the intervention to 24 hours after completion of the intervention or drain removal, as applicable, The intraoperative blood loss will be measured by determining the volume of blood and fluid removal through suction into the collection container (waste box and/or cell saver) and the estimated blood loss into swabs and towels during the procedure, per the anesthesiologist’s record. Post-operatively, blood loss will be determined by the drainage volume collected, which will likely consist mainly of drainage fluid via vacuum or gravity drain, as applicable. Transfusion requirements The type and number of units and amount (in mL) of blood products will be recorded. Furthermore, also salvage of blood obtained from autologous transfusion systems, e.g. cell savers, will be recorded. In addition, the type and amount of fluid replacement and volume expanders will be recorded as concomitant medication (e.g. amount and number of units of salvaged blood, red blood cells, platelets and other blood products transfused). Bleeding Episodes Any clinically relevant bleeding episodes, as well as the need for any further surgical interventions, are to be recorded. Study subjects will be closely monitored for the occurrence of | — |
Countries
Belgium, Bulgaria, Germany, Lithuania, Netherlands, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactEli Taube
Baxalta Innovations GmbH
Outcome results
None listed