Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Emicizumab
Intervention description: Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Healthy volunteers: No

Summary:

      This Phase IV, multicenter study will evaluate whether participants with Hemophilia A (PwHA)
      with or without inhibitors receiving emicizumab prophylaxis can safely undergo minor surgical
      procedures without additional prophylactic bypassing agents (BPA; for participants with
      inhibitors) or factor VIII (FVIII; for participants without inhibitors).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any age (newborn and older)

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Diagnosis of hemophilia A and current or history of an inhibitor (Bethesda titer ≥0.6
             Bethesda units) and currently using bypassing agents (BPAs) for breakthrough bleeds
             (for PwHA with inhibitors)

          -  Diagnosis of hemophilia A and no history of an inhibitor (Bethesda titer <0.6 Bethesda
             units), or a history of an inhibitor that has been tolerized for >5 years and using
             FVIII for breakthrough bleeds (for PwHA without inhibitors)

          -  Plan to receive at least 4 loading doses of emicizumab and been adherent to emicizumab
             prophylaxis by the time of surgery

          -  Undergoing minor surgery within 60 days of study enrollment. Other minor surgical
             procedures could be included upon consultation and approval of Medical Monitor, but
             examples include central venous catheter insertion/removal/replacement, simple dental
             extractions, colonoscopy, cystoscopy, or endoscopy with biopsy, excisional skin biopsy

          -  Must plan to continue emicizumab prophylaxis for at least 1 month after surgery

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of <1% per year during the study period

        Exclusion Criteria:

          -  Diagnosis of a bleeding disorder other than hemophilia A

          -  Participants who have been tolerized to Factor VIII products (for PwHA with
             inhibitors)

          -  Tolerized to FVIII products for <5 years (for PwHA without inhibitors)

          -  Using FVIII products to treat breakthrough bleeds (for PwHA with inhibitors)

          -  Treatment with BPAs or FVIII within 24 hours prior to surgical procedure

          -  Undergoing a major surgical procedure

          -  Previous (in the past 12 months) or current treatment for thromboembolic disease (with
             the exception of previous catheter-associated thrombosis for which anti-thrombotic
             treatment is not currently ongoing) or current signs of thromboembolic disease

          -  Other conditions (e.g., certain autoimmune diseases, including but not limited to
             diseases such as systemic lupus erythematosus, inflammatory bowel disease, and
             antiphospholipid syndrome) that may increase the risk of bleeding or thrombosis

          -  Patients who are at high risk for thrombotic microangiopathy (TMA), e.g., have a
             previous medical or family history of TMA, in the investigator's judgment

          -  Would refuse treatment with blood or blood products, if necessary

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the participant's safe participation in and
             completion of the study

          -  Pregnant or lactating, or intending to become pregnant during the study; women of
             childbearing potential must have a negative serum pregnancy test result within 7 days
             before Study Day 1

          -  Treatment with any of the following: An investigational drug to treat or reduce the
             risk of hemophilic bleeds within 5 half-lives of last drug administration before Study
             Day 1; A non-hemophilia-related investigational drug within the last 30 days or 5
             half-lives before Study Day 1 (whichever is longer); An investigational drug
             concurrently

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known human immunodeficiency virus (HIV) infection with CD4 count < 200
             cells/microlitre within 24 weeks prior to enrollment