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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Severe hemophilia A (Factor VIII (FVIII) <1%) determined by central laboratory.
- <12 years old at the time of screening.
- Participants aged =6 to <12 years of age have been previously treated with
plasma-derived and/or recombinant Factor VIII (rFVIII) concentrate(s) for a minimum of
150 exposure days (EDs) (based on the participant's medical records).
- Participants <6 years of age have been previously treated with plasma-derived and/or
rFVIII concentrate(s) for at least 50 EDs (based on the participant's medical
records).
- Participant is human immunodeficiency virus (HIV) negative; or HIV positive with
stable disease and CD4+ count of =200 cells/mm^3, as confirmed by central laboratory.
- Participant and/or legal representative accepts prophylactic treatment over a period
of 6 months.
- Participant and/or the legal representative is willing and able to comply with the
requirements of the protocol.
Exclusion Criteria:
- Participant has detectable FVIII inhibitory antibodies (=0.4 Bethesda Units (BU) using
the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at
screening.
- Participant has a history of FVIII inhibitory antibodies (=0.4 BU using the Nijmegen
modification of the Bethesda assay or =0.6 BU using the Bethesda assay) at any time
prior to screening.
- Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene
glycol (PEG), or Tween 80.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other
than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
- Participant's platelet count is <100,000/µL.
- Participant has severe chronic hepatic dysfunction (eg, =5 times upper limit of normal
(ULN) alanine aminotransferase (ALT), as confirmed by central laboratory at screening,
or a documented international normalized ratio (INR) >1.5).
- Participant has severe renal impairment (serum creatinine >1.5 times ULN).
- Participant is scheduled to receive during the course of the study, an
immunomodulating drug (eg, corticosteroid agents at a dose equivalent to
hydrocortisone >10 mg/day, or a-interferon) other than anti-retroviral chemotherapy.
- 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.
- 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.
- Participant 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.
- Participant's legal representative is 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.
Age minimum:
N/A
Age maximum:
11 Years
Gender:
All
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Secondary Outcome(s)
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Pharmacokinetics (PK): Incremental Recovery (IR)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Pharmacokinetics (PK): Clearance (CL)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Consumption of BAX 855: Number of Infusions Per Bleeding Episode
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
[Time Frame: Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)]
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Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Annualized Bleeding Rate (ABR)
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to 8 Hours Post-infusion (AUC0-8)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
[Time Frame: Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)]
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Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Number of Participants With Clinically Significant Changes in Vital Signs
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Pharmacokinetics (PK): Mean Residence Time (MRT)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant
[Time Frame: During prophylaxis period of 6 months or = 50 EDs, whichever occurs last]
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Non-serious Adverse Events Possibly or Probably Related to BAX 855
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)
[Time Frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.]
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Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to 8 Hours Post-infusion Per Dose, (AUC0-8/Dose)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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Pharmacokinetics (PK): Plasma Half-life (T1/2)
[Time Frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4]
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