SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

NCT04563520 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: STUDY000008042025P010684
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hemophilia A

Keywords

hemostatic efficacy; safety; prothrombin complex concentrate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of serious adverse events

  up to 1 year

• Number of serious bleeding episodes

  up to 1 year

• Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)

  up to 1 year

Study Arms (1)

Experimental treatment

EXPERIMENTAL

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: Emicizumab; Drug: FEIBA; Drug: rFVIIa

Interventions

Emicizumab DRUG

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.

Also known as: ACE910, Hemlibra and RO5534262

Experimental treatment

FEIBA DRUG

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.

Also known as: Activated prothrombin complex (aPCC), Anti-Inhibitor Coagulant Complex

Experimental treatment

rFVIIa DRUG

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.

Also known as: Recombinant activated factor VII

Experimental treatment

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (2)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

emicizumab; anti-inhibitor coagulant complex; recombinant FVIIa

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Robert Sidonio, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Sidonio, MD

CONTACT

404-785-1637; robert.sidonio.jr@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 24, 2020
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (2)