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

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

The purpose of the aPCC-emicizumab safety study is to investigate the hemostatic efficacy as measured by thrombin generation, of a low personalized dose of aPCC (FEIBA) in children and adults with hemophilia A and inhibitors on emicizumab prophylaxis.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: rFVIIa; Drug: Emicizumab; Drug: FEIBA

Detailed Description

Hemophilia A (HA) is a congenital bleeding disorder caused by deficient or dysfunctional factor VIII (FVIII) which leads to bleeding correlated with factor deficiency severity. Patients with HA develop recurrent bleeds into joints and soft tissues that culminate into debilitating arthropathy and long-term morbidity.

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 overall objective is to determine whether the thrombin generation assay can be used to personalize a dose of aPCC that could be used in a future study during an acute bleeding event and peri-surgical prophylaxis in children and adults with hemophilia A and inhibitors on emicizumab primary prophylaxis.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Robert Sidonio, MD; Phone Number: 404-785-1637; Email: robert.sidonio.jr@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Children's Healthcare of Atlanta
      • Contact: Robert Sidonio, MD; Phone Number: 4047851637; Email: robert.sidonio.jr@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Moderately severe hemophilia A, defined as FVIII level <0.05 IU/mL before 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 (Legally Authorized Representative) or the 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)
• Had an active bleed requiring factor therapy at screening
• Previous or current treatment for thromboembolic disease or signs of thromboembolic disease (excluding previously resolved line-associated thrombosis)
• Had a surgical procedure 14 days before screening
• Conditions that may increase the risk of bleeding or thrombosis
• If the patient is treated with rFVIIa or aPCC seven days before screening
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Had current use of any medication other than emicizumab that could affect the coagulation system.
• Known HIV infection with CD4 count <200 cells/µL within 24 weeks before screening. Testing is 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 an additional risk, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental treatment; Participants will have a first/baseline thrombin generation assay (TGA) sample (to be processed within 60 minutes), followed by an infusion at 15 U/kg dose of aPCC, and provide a second TGA sample 15-30 minutes after to be processed within 60 minutes. If required, a subsequent TGA sample will be obtained upon a 25 U/kg dose of aPCC to be processed within 60-90 minutes.

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.; Other Names: Recombinant activated factor VII; Drug: Emicizumab; HEMLIBRA® is a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors.; Other Names: 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, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes. The max dose allowed for aPCC will be 50 U/kg dose given at a single visit.; Other Names: Anti-Inhibitor Coagulant Complex; Activated prothrombin complex (aPCC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombin generation capacity after aPCC (FEIBA) infusion	Thrombin generation capacity from up to two escalating doses of aPCC will be measured using a thrombin generation assay at baseline and up to 30 minutes after FEIBA infusion.	Baseline and up to 30 minutes after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of serious adverse events	Number of serious adverse events will be recorded	up to 1 year
Number of serious bleeding episodes	Number of serious bleeding episodes will be recorded	up to 1 year
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 1 year

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: Principal Investigator: Robert Sidonio, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: safety; hemostatic efficacy; prothrombin complex concentrate
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Hemophilia B; emicizumab; recombinant FVIIa; anti-inhibitor coagulant complex
• Other Study ID Numbers: STUDY00000804; 2025P010684 (Other Identifier: Emory Insight Humans IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after de-identification, will be available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• 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