Baxalta 261203 PUP

Principal Investigator: Hassan Yaish
Keywords: Hemophilla A , Safety , BAX855 Department: Pediatric Administration
IRB Number: 00092503 Co Investigator: Richard Lemons
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Heather Gallo

Brief Summary

Study Purpose
The purpose of the study is to investigate the safety, immunogenicity and hemostatic efficacy of PEGylated recombinant FVIII (BAX 855) in PUPs <6 years of age with severe hemophilia A (baseline FVIII level < 1%) and < 3 EDs to ADVATE, BAX 855 or FFP .
Primary Objective
The primary objective of the study is to determine the safety including immunogenicity of BAX 855 based on the incidence of inhibitor development to FVIII (≥ 0.6 BU/mL using the Nijmegen modification of the Bethesda assay).

Secondary Objectives


  • To determine the immunogenicity of BAX 855 in terms of binding IgG and IgM
    antibodies to FVIII, PEG-FVIII and PEG
  • To determine the safety of BAX 855 based on AEs and SAEs
Hemostatic Efficacy
  • To assess the efficacy of prophylactic treatment with BAX 855
  • To characterize the efficacy of BAX 855 in the control of bleeding episodes
  • To evaluate the efficacy of BAX 855 for perioperative management, if surgery is required
  • To determine incremental recovery (IR) of BAX 855 at baseline and over time
  • To determine abbreviated half-life at baseline (optional)

ITI Objectives

  • To evaluate efficacy and safety of ITI with BAX 855
  • To determine the rate of success, partial success and failure of ITI with BAX 855

Exploratory Objectives

  • To determine the potential correlation of FVIII inhibitor development and the
    presence of high affinity IgG(1-4) FVIII binding antibodies at screening and/or
    during the study
  • To determine epigenetic markers indicative of immune cell populations such as
    regulatory T cells, NK cells, Th17 cells, Tfh cells and other lymphoid cell
    populations which potentially contribute to the regulation of FVIII inhibitor
    development, at screening and during the study
Additional exploratory objective for ITI
  • To determine the potential correlation of the course of high affinity IgG (1-4)
    FVIII binding antibodies and epigenetics with the outcome of ITI therapy

Inclusion Criteria

Inclusion Criteria

Subjects who meet ALL of the following criteria are eligible for this study:
1. Subject is < 6 years old at the time of screening

2. Subject is previously untreated with < 3 EDs to ADVATE, BAX 855 or Fresh Frozen Plasma (FFP) at any time prior to screening

3. Subject has severe hemophilia A (FVIII < 1%) as determined by the central laboratory, or a historical FVIII level < 1% as determined at any local laboratory, optionally supported by an additional FVIII gene mutation consistent with severe hemophilia A

4. Subject is immune competent with a CD4+ count > 200 cells/mm3, as confirmed by the 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

Exclusion Criteria

Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
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, BAX 855x or FFP, or was administered ADVATE, BAX 855 or FFP for ≥ 3 EDs at any time prior to screening
5. Subject has received any kind of blood-transfusion such as packed red blood cells (PRBC), platelets or plasma at any time prior to screening
6. The subject’s weight is < 5 kgxi
7. Subject’s platelet count is < 100,000/mL
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 (< 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 α-interferon) other than anti-retroviral chemotherapyxii
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.
Additional exclusion criteria for Part B (ITI)
1. Spontaneous disappearance of the inhibitor prior to ITI
2. FVIII inhibitor titer ≥ 0.6 BU is not confirmed by a second new blood sample and determined at the central laboratory
3. Inability or unwillingness to comply with the protocol
x BAX 855 refers to commercial BAX 855 in those countries where licensed at the time the study is
xi If a subject is close to 5 kg at screening and it is anticipated that he will have reached a weight of at
least 5 kg at the baseline visit, the subject is eligibile for participation.
xii The use of systemic immunomodulating drugs, eg, with anti-CD20 chimeric monoclonal antibody
rituximab, as part of ITI therapy with BAX 855 is permitted.