Study of rFVIIIFc for ITI in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies

This is an open-label, single-arm, interventional multi-center study designed to explore ITI
performed with recombinant coagulation factor VIII Fc fusion protein (rFVIIIFc) within a
timeframe of 60 weeks in patients with severe haemophilia A, who have failed previous
attempts at tolerization including use of immunosuppressants.

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