Clinical trial: Safety, Immunogenicity and Hemostatic Efficacy of PEGylated Recombinant FVIII (BAX 855) in Previously Untreated Patients (PUPs) < 6 Years of Age With Severe Hemophilia A (NCT02615691)

Eligibility criteria:
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 CD4+ count > 200 cells/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 (≥ 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 >2 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 kg at the baseline visit

          7. Participant's platelet count is < 100,000/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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.

Subject must be at most 5 Years

Patient description (medical language): A 20-year-old man comes to the emergency due to bleeding after a tooth extraction.  The bleeding has persisted for approximately 30 minutes despite constant direct pressure.  He is a known case of Hemophilia type A treated with FVIII. Blood pressure is 95/60 mm Hg and pulse is 105/min. His weight is 70 Kg. Family history is positive for Hemophilia type A in his maternal uncle. He also has a lipoma on his left arm which he plans to remove surgically. His FVIII activity is 40%.

Patient description (patient's own words): I got my tooth extracted and I could not stop bleeding for 30 min. I'm a 20 yo dude but I have Hemophilia type A treated with FVIII. My blood pressure was 95/60 and my pulse 105/min. I'm 70 kg. My uncle on my mom's side also has type A hemophilia. I also have a fatty swelling on my left arm and I was supposed to remove it. My FVIII activity was 40%.

Does the patient match the trial criteria? Contradiction