SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

Hemophilia A Clinical Trial

— SAFE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04563520
• Other study ID #: STUDY00000804
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: Emory University
• Contact: Robert Sidonio, MD
• Phone: 404-785-1637
• Email: robert.sidonio.jr[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of serious adverse events	Number of serious adverse events will be recorded	up to 2 years
Primary	Number of serious bleeding episodes	Number of serious bleeding episodes will be recorded	up to 2 years
Primary	Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)	Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded	up to 2 years
Secondary	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	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.	up to 2 years