SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

Brief Title

SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

Official Title

aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)

Brief Summary

      The purpose of the aPCC-emicizumab safety study is to prospectively investigate the safety
      and hemostatic efficacy of a personalized dose of aPCC in children and adults with hemophilia
      A and inhibitors on emicizumab prophylaxis during acute bleeding events or prior to
      procedures.

Detailed Description

      The previous standard of care for high titer antibody eradication in hemophilia A (HA)
      included a labor-intensive, immune tolerance induction (ITI) regimen administered with
      concomitant bypassing agent (BPA) prophylaxis, either daily recombinant activated factor VII
      (rFVIIa) or at least 3 non-consecutive days of activated prothrombin complex concentrate
      (aPCC) given intravenously (IV) each week.

      The purpose of the aPCC-emicizumab safety study is to prospectively investigate the safety
      and hemostatic efficacy of a personalized dose of aPCC in children and adults with hemophilia
      A and inhibitors on emicizumab prophylaxis during acute bleeding events or prior to
      procedures.

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Number of serious adverse events

Secondary Outcome

 Number of infusions of aPCC required to achieve hemostatic efficacy for treatment of an acute bleeding episode, or prevention of bleeding with emergent and non-emergent procedures

Condition

Hemophilia A

Intervention

aPCC-emicizumab

Study Arms / Comparison Groups

 Experimental treatment

Description:  Personalized dose of aPCC-emicizumab will be administered to participants. The max dose allowed for aPCC will be 25 U/kg/dose every 8 hours, for no more than 72 hours without further discussion with the PI. If there is less than a "good' response in bleed event response efficacy as stated above at 48 hours or less than "moderate" for surgical event control, the local PI can consider the use of thrombin generation guided rFVIIa with max dose no more than 90 µg/kg/dose every 8 hours for 72 hours, with wean to occur for no more than 7 total days without further discussion with the PI.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

March 2023

Completion Date

September 2023

Primary Completion Date

September 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Moderately severe hemophilia A, defined as FVIII level <0.02 IU/mL in the central
             laboratory prior to development 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 washout
             within 2 years of enrollment

          -  Parent/guardian (caregiver henceforth) or patient has provided written 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 at
             screening (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)

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

          -  Conditions that may increase risk of bleeding or thrombosis

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known HIV infection with CD4 count <200 cells/µL within 24 weeks prior to screening.
             Testing 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 previous medical/family
             history of TMA), in the investigator's judgment

          -  Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
             interfere with the conduct of the study, may pose additional risk, or would, in the
             opinion of the investigator, preclude the participant's safe participation in and
             completion of the study

          -  Every effort will be made to include participants that are considering minor and major
             procedures over the next 2 years to capture this important data with the goal of 10
             procedures.

Gender

All

Ages

6 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Robert Sidonio, MD, 404-785-1637, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT04563520

Organization ID

STUDY00000804

Responsible Party

Principal Investigator

Study Sponsor

Emory University

Collaborators

 Takeda Pharmaceuticals North America, Inc.

Study Sponsor

Robert Sidonio, MD, Principal Investigator, Emory University

Verification Date

January 2023