BAX 826 Dose-Escalation Safety Study

A Phase 1, Prospective, Open Label, Two Period, Fixed Sequence, Dose-Escalation Study of the PK and Safety of BAX 826 (PSA-rFVIII) in Previously Treated Patients With Severe (FVIII <1%) Hemophilia A

1. To assess tolerability and safety of BAX 826 after a single infusion in previously treated patients (PTPs) with severe hemophilia A
2. To determine the pharmacokinetic (PK) parameters of BAX 826 compared to ADVATE
3. To evaluate immunogenicity of polysialic acid linked to Factor VIII (FVIII)

Inclusion Criteria:

1. Previously treated male participants aged 18 to 65 years (inclusive) at the time of screening
2. Diagnosis of severe hemophilia A (Factor VIII level <1%)
3. Previously treated with FVIII concentrates for ≥150 documented Exposure Days (EDs)
4. Karnofsky performance score of ≥60
5. Human immunodeficiency virus negative (HIV-); or HIV+ with stable disease
6. Hepatitis C virus negative (HCV-); or HCV+ with chronic stable hepatitis as assessed by the investigator
7. Able to understand and have provided written informed consent including signature on an informed consent form (ICF) approved by an ethics committee (EC)
8. Have provided written authorization for use and disclosure of protected health information
9. Agree to abide by the study schedule and to return for the required assessments
10. Willing and able to comply with the requirements of the protocol

Exclusion Criteria:

1. Detectable FVIII inhibitor at screening, with a titer ≥0.6 Bethesda Unit (BU)
2. Documented history of FVIII inhibitors with a titer ≥0.4 BU at any time prior to screening
3. Known clinical hypersensitivity towards mouse or hamster proteins or to polysialic acid (PSA)
4. Scheduled elective surgery during study participation
5. Severe chronic hepatic dysfunction
6. Severe renal impairment
7. Currently receiving, or has recently received (less than 3 months prior to study participation), or is scheduled to receive during the course of the study, other PSA-ylated drugs
8. Have received another investigational drug within 30 days prior to study entry and/or is scheduled to receive additional investigational drug during the course of the study in the context of another investigational drug study
9. Diagnosis of an inherited or acquired hemostatic defect other than hemophilia A
10. Currently receiving, or scheduled to receive during the course of the study, an immune-modulating drug other than antiretroviral chemotherapy
11. Has a clinically significant medical, psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect the safety or compliance of the participant during the study
12. Is a family member or employee of the investigator