Protocol Summary

Protocol No.: OCR17544

Sponsor Protocol No.: ML39791

Protocol Title.: Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures

Principal Investigator: Wynn, Tung

Objective: 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).

Phase: Phase IV

Age Group: Both

Age: N/A - N/A

Gender: All

Scope: National

Treatment:

Experimental: Cohort 1 - PwHA With Inhibitors: Emicizumab Prophylaxis
All eligible participants with Hemophilia A (PwHA) with inhibitors will receive emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (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 they continue to derive sufficient benefit. Participants must have received all loading doses prior to surgery and plan to continue emicizumab for a minimum of 1 month after surgery. Dosing should be adjusted if the participant has a significant change in body weight.

Experimental: Cohort 2 - PwHA Without Inhibitors: Emicizumab Prophylaxis
All eligible participants with Hemophilia A (PwHA) without inhibitors will receive emicizumab via SC injection at a loading dose of 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 they continue to derive sufficient benefit. Participants must have received all loading doses prior to surgery and plan to continue emicizumab for a minimum of 1 month after surgery. Dosing should be adjusted if the participant has a significant change in body weight.

Detailed Eligibility:

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 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

Applicable Conditions:

  • Pediatric Hemophilia A
  • Participation Institution:

  • UF Gainesville : Melissa Lingis
  • Contact:
    Melissa Lingis
    Phone: +1 352-294-8556
    Email: melissa.lingis@peds.ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT03361137