Alphanate in Immune Tolerance Induction Therapy

Male subjects <8 years of age presenting with an inhibitor titer >0.6 to <10 Bethesda Units
(BU) will be screened before the planned start of ITI treatment. Subjects continuing to meet
the entrance criteria will enter the ITI Treatment Phase and receive daily doses of Alphanate
100 IU/kg/day for up to 33 months, with a one-time option to increase to a dosing regimen of
200 IU/kg/day at any time after 90 days of ITI treatment.

Subjects will continue to receive their daily Alphanate dose for up to 33 months until the
titer is negative (<0.6 BU) on 2 consecutive assessments and treatment success is confirmed
by FVIII:C pharmacokinetic assessments, at which time they will enter the 12 month
Prophylactic Phase.

In addition, subjects who have achieved partial immune tolerance at the completion of 33
months of ITI treatment will enter the 12-month Prophylactic Phase. Subjects who do not
achieve partial immune tolerance at the completion of 33 months of ITI treatment will be
discontinued as treatment failures.

The Prophylactic Phase begins with an 8 week taper period for subjects tolerized with 100
IU/kg/day or with a 12-week taper period for subjects tolerized with 200 IU/kg/day to bring
the dose down in a step-wise manner to a prophylactic dose of Alphanate 50 IU/kg every other
day or 3 times per week, at the investigator's discretion. During the Prophylactic Phase,
subjects will be monitored monthly for the first 4 months and then every 2 months for the
remaining 8 months to assess sustainability of immune tolerance.

Inclusion Criteria:

- The subject has a documented diagnosis of severe congenital hemophilia A with FVIII:C
<1% of normal.

- The subject is a male up to 8 years (and at least 2 years of age if in India) at the
Baseline Visit.

- The subject's documented historical peak inhibitor titer is ≥10 BU and ≤200 BU.

- The subject has an inhibitor titer >0.6 BU and <10 BU at Screening.

- The subject has had a delay ≤24 months from the date of diagnosis of the inhibitor to
the start of the subject's ITI treatment.

Exclusion Criteria:

- The subject has acquired factor VIII (FVIII) deficiency.

- The subject has previously received ITI treatment.

- The subject has a recent (within 1 month) history of central line infection at the
time of Screening.

- The subject has a high risk of cardiovascular, cerebrovascular, or thromboembolic
event as judged by the investigator.

- The subject is currently undergoing treatment with immunosuppressive drugs (eg,
systemic corticosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin,
interferon, or the use of a protein A column or plasmapheresis and is unwilling to
discontinue these treatments starting at the screening visit.

- The subject has a known infection with human immunodeficiency virus (HIV) or has
clinical signs and symptoms consistent with current HIV infection.

- The subject has a known previous infection with hepatitis B virus (HBV) or hepatitis C
virus (HCV) or has clinical signs and symptoms consistent with current HBV or HCV
infection.

- The subject has significant proteinuria, has a history of acute renal failure or
severe renal impairment (blood urea nitrogen or creatinine >2 times the upper limit of
normal), or is receiving dialysis at Screening.

- The subject has a value of aspartate transaminase or alanine aminotransferase >2 times
the upper limit of normal at Screening.

- The subject has clinical evidence of any significant acute or chronic disease that, in
the opinion of the investigator, may interfere with successful completion of the trial
or place the subject at undue medical risk.

- The subject has a history of anaphylaxis or severe systemic reaction to any plasma
derived or other blood products.