A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A

Phase 3, Prospective, Multi-center, Open Label Study to Investigate Safety, Immunogenicity and Hemostatic Efficacy of PEGylated Factor VIII (BAX 855) in Previously Untreated Patients (PUPs) < 6 Years With Severe Hemophilia A (FVIII < 1%)

This study is for young children with severe hemophilia A who have previously not been treated with BAX855 or other FVIII concentrates.

The main aim of the study is to check for side effects from treatment with BAX855. This includes the buildup of antibodies against FVIII which may stop BAX855 from working properly. Another aim is to learn how well BAX855 controls bleeding.

In this study, the children can receive BAX855 either as preventative treatment (prophylaxis), or as needed to treat bleeding (on-demand).

In case a participant develops antibodies, treatment will be provided as part of the study.

Inclusion Criteria

1. Participant is <6 years old at the time of screening.
2. Participant is previously untreated with <3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion at any time prior to screening.
3. Participant has severe hemophilia A (Factor VIII (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. Participant is immune competent with a cluster of differentiation 4 (CD4+) count > 200 cells per cubic millimeter (mm^3), 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 (immune tolerance induction [ITI]).

1. Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion.

2. Participant has a confirmed positive high titer inhibitor (> 5.00 Bethesda unit (BU)) or has a positive confirmed low titer inhibitor (greater than or equal to [>=] 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with

   1. poorly controlled bleeding despite increased BAX 855 doses, or
   2. requires bypassing agents to treat bleeding.

Exclusion Criteria

1. Participant has detectable FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Participant 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. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
4. Participant has been previously treated with any type of FVIII concentrate other than ADVATE or BAX 855, or was administered ADVATE, BAX 855 or plasma transfusion for >=3 EDs at any time prior to screening.
5. Participant receives > two EDs of ADVATE in total during the periods prior to enrollment and during the screening period, until the baseline infusion.
6. The participant's weight is anticipated to be <5 kilogram (kg) at the baseline visit.
7. Participant's platelet count is <100,000 per milliliter (mL).
8. Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG) or Tween 80.
9. Participant has severe chronic hepatic dysfunction (eg, >5 times upper limit of normal alanine aminotransferase [ALT], aspartate aminotransferase [AST], or a documented international normalized ratio [INR] >1.5) in his medical history or at the time of screening.
10. Participant has severe renal impairment (serum creatinine >1.5 times the upper limit of normal).
11. Participant 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. Participant 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 chemotherapy.
13. Participant has participated in another clinical study involving an investigational product (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 participant safety or compliance.
15. Parent, legally authorized representative or participant 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.