Alphanate in Immune Tolerance Induction Therapy
Condition: Hemophilia A, Congenital
MeSH terms: Hemophilia A
Intervention: Alphanate
Intervention description: Bolus IV injection.
Intervention MeSH terms: Factor VIII
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Male
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Factor VIII; von Willebrand Factor; Plasma-derived; Inhibitors; Immune tolerance induction (ITI); Antibodies; Hemophilia A

Summary:

      This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label
      study, planned in of approximately 25 male participants with congenital hemophilia A who will
      receive their first (primary) immune tolerance induction (ITI) treatment with alphanate.

      The study consists of 2 phases:

        -  An ITI Treatment Phase in which all eligible participants will receive ITI treatment
           with alphanate for a period of up to 33 months. Upon confirmation of complete immune
           tolerization, participants will then enter a 12-month Prophylactic Phase. If, after 33
           months of ITI, a participants has achieved partial immune tolerance, the participants
           will enter a 12-month Prophylactic Phase.

        -  A 12-month Prophylactic Phase for all participants who meet the criteria for complete or
           partial success to continue on a prophylactic dosing regimen of alphanate. Due to
           limited enrollment, this study was early terminated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has a documented diagnosis of severe congenital hemophilia A with FVIII:C
             <1% of normal.

          -  The subject is a male <12 years (and at least 2 years of age if in India) at the
             Baseline Visit.

          -  The subject's documented historical peak inhibitor titer is ≥5 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.