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SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis (SAFE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04563520
Recruitment Status : Not yet recruiting
First Posted : September 24, 2020
Last Update Posted : January 6, 2023
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Robert Sidonio, Emory University

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.

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: aPCC-emicizumab Drug: FEIBA Drug: rFVIIa Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)
Estimated Study Start Date : March 2023
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Hemophilia

Arm Intervention/treatment
Experimental: Experimental treatment
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.
Drug: aPCC-emicizumab
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.
Other Name: ACE910, Hemlibra and RO5534262

Drug: FEIBA
FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia patients with inhibitors for: control and prevention of bleeding episodes, perioperative management, routine prophylaxis to prevent or reduce the frequency of bleeding episodes. If there is less than a "good' response in bleed event at 48 hours or less than "moderate" for surgical event control, the local PI can consider the use of thrombin generation guided rFVIIa with a max dose of no more than 90 µg/kg/dose every 8 hours for 72 hours, with wean to occur for no more than 7 total days.
Other Name: Anti-Inhibitor Coagulant Complex

Drug: rFVIIa
rFVIIa is a coagulation factor VIIa concentrate indicated for the treatment and control of bleeding episodes occurring in adults and adolescents with hemophilia with inhibitors.




Primary Outcome Measures :
  1. Number of serious adverse events [ Time Frame: up to 2 years ]
    Number of serious adverse events will be recorded

  2. Number of serious bleeding episodes [ Time Frame: up to 2 years ]
    Number of serious bleeding episodes will be recorded

  3. Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) [ Time Frame: up to 2 years ]
    Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded


Secondary Outcome Measures :
  1. 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 [ Time Frame: up to 2 years ]
    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 will be recorded.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04563520


Contacts
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Contact: Robert Sidonio, MD 404-785-1637 robert.sidonio.jr@emory.edu

Locations
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United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Contact: Robert Sidonio, MD    404-785-1637    robert.sidonio.jr@emory.edu   
Emory University Hospital
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Takeda Pharmaceuticals North America, Inc.
Investigators
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Principal Investigator: Robert Sidonio, MD Emory University
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Responsible Party: Robert Sidonio, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT04563520    
Other Study ID Numbers: STUDY00000804
First Posted: September 24, 2020    Key Record Dates
Last Update Posted: January 6, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after de-identification, will be available
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Robert Sidonio, Emory University:
hemostatic efficacy
safety
prothrombin complex concentrate
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Coagulants
Anti-inhibitor coagulant complex