Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Recombinant coagulation factor (rFVIIIFc)
Intervention description: rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement
administered intravenously.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Male
Healthy volunteers: No
Keywords: ITI; rFVIIIFc; Immune Tolerance Induction

Summary:

      The primary purpose of this study is to describe the outcome of Immune Tolerance Induction
      (ITI) treatment performed with rFVIIIFc within a timeframe of 60 weeks in patients with
      haemophilia A who have failed previous attempts at tolerization.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed and dated informed consent provided by the patient, or the patient's legally
             authorized representative for patients under the legal age. Assent should be obtained
             from pediatric patients according to local regulations

          2. Male patients of any age diagnosed with severe haemophilia A, as confirmed from the
             medical record

          3. Previously treated with any plasma-derived or recombinant conventional or extended
             half-life FVIII

          4. Diagnosed with high titer inhibitors (historical peak ≥5 Bethesda units (BU)/mL
             according to medical records)

          5. Inhibitor titer >0.6 BU at screening

          6. Failed previous ITI attempt(s) with any plasma-derived or recombinant conventional or
             extended half-life FVIII including the use of immunosuppressant The attempt should be
             documented in the medical records and have the following characteristics:

               -  A minimum FVIII dose equivalent to the low dose arm of the International ITI
                  study (50 IU/kg, 3 times/week)

               -  A minimum ITI treatment period of 33 months or

               -  Shorter than 33 months if no downward trend of at least 20% in the inhibitor
                  titer in a 6-month period after the initial 3 months of the ITI treatment

          7. All patients must practice effective contraception during the study and for 3 months
             after their last dose of study treatment

        Exclusion Criteria:

          1. Other coagulation disorder(s) in addition to haemophilia A

          2. History of hypersensitivity reactions associated with any rFVIIIFc administration

          3. High risk of cardiovascular, cerebrovascular, or other thromboembolic events, as
             judged by the investigator

          4. Planned major surgery to be deferred after study completion. Minor surgery such as
             tooth extraction or insertion/replacement of central venous access device is allowed.

          5. Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to
             screening. Exceptions to this include: ribavirin for treatment of Hepatitis C virus
             (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no
             more than 7 days within 12 weeks prior to Day 1) and/or inhaled steroids

          6. Abnormal renal function (serum creatinine >2.0 mg/dL) as assessed by local lab

          7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper
             limit of normal (ULN) as assessed by local lab

          8. Serum total bilirubin >3 × ULN as assessed by local lab

          9. Cluster of differentiation 4 (CD4) lymphocytes ≤200 mm3 if known as HIV antibody
             positive at Screening

         10. Viral load of ≥400 copies/mL if known HIV antibody positive at Screening

         11. Patients with a documented history of alcohol or substance abuse within 12 months
             prior to randomization

         12. Previous inclusion in this study

         13. Participation in another concurrent clinical interventional study within 30 days of
             screening or intake of an investigational drug within five half-lives of that
             investigational drug has passed

         14. Foreseeable inability to cooperate with given instructions or study procedures

         15. Presence of any medical or psychological condition or laboratory result that in the
             opinion of the investigator can interfere with the patient's ability to comply with
             the protocol requirements or makes the patient not appropriate for inclusion to the
             study and treatment with rFVIIIFc