SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

Inclusion Criteria:

• Moderately severe hemophilia A, defined as FVIII level <0.05 IU/mL beforedevelopment of an inhibitor

• Age ≥6 years of age at time of informed consent

• Documented on 2 occasions a high titer inhibitor (>5 BU/mL) with a 72-hour washoutwithin 2 years of enrollment

• Parent/guardian (Legally Authorized Representative) or the patient has providedwritten informed consent

• Adequate hematologic function (Hgb >8 g/dL and platelet count >100,000 µL)

• Adequate hepatic function (total bilirubin ≤1.5 x ULN and both AST/ALT ≤3x ULN atscreening (excluding known Gilbert's)

• Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)

Exclusion Criteria:

• Inherited or acquired bleeding disorder other than hemophilia A excluding low VWF (>30% VWF:RCo or VWF:GP1bm)

• Had an active bleed requiring factor therapy at screening

• Previous or current treatment for thromboembolic disease or signs of thromboembolicdisease (excluding previously resolved line-associated thrombosis)

• Had a surgical procedure 14 days before screening

• Conditions that may increase the risk of bleeding or thrombosis

• If the patient is treated with rFVIIa or aPCC seven days before screening

• History of clinically significant hypersensitivity associated with monoclonalantibody therapies or components of the emicizumab injection

• Had current use of any medication other than emicizumab that could affect thecoagulation system.

• Known HIV infection with CD4 count <200 cells/µL within 24 weeks before screening.Testing is not required if <35 years of age.

• Use of systemic immunomodulators at enrollment or planned use during the study

• Participants who are at high risk for TMA (for example, have a previousmedical/family history of TMA), in the investigator's judgment

• Concurrent disease, treatment, or abnormality in clinical laboratory tests thatcould interfere with the conduct of the study, may pose an additional risk, orwould, in the opinion of the investigator, preclude the participant's safeparticipation in and completion of the study