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RecruitingNCT04563520SAFEUpdated Aug 21, 2026

SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

A Phase 3 interventional study of Emicizumab and FEIBA in Hemophilia A, sponsored by Emory University. Recruiting at 2 sites in United States. Open to participants aged 6 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.

Sponsored by Emory University · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
5
Allocation
Not applicable
Ages
6 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Hemophilia A

Keywords

  • hemostatic efficacy
  • safety
  • prothrombin complex concentrate
03

Who can participate

Ages eligible
6 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
5 participants (estimated)

Study arms

  • 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: Emicizumab · Drug: FEIBA · Drug: rFVIIa

Interventions

  • DrugEmicizumab

    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

  • DrugFEIBA

    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

  • DrugrFVIIa

    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

05

What researchers measure

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.

    Time frame: Baseline and up to 30 minutes after infusion

Secondary outcomes

  1. Number of serious adverse events

    Number of serious adverse events will be recorded

    Time frame: up to 1 year

  2. Number of serious bleeding episodes

    Number of serious bleeding episodes will be recorded

    Time frame: up to 1 year

  3. Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)

    Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded

    Time frame: up to 1 year

06

Study locations

2 of 2 sites recruiting
  • Children's Healthcare of Atlanta
    Atlanta, Georgia 30322, United States
    Recruiting
  • Emory University Hospital
    Atlanta, Georgia 30322, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — All of the individual participant data collected during the trial, after de-identification, will be available

Supporting information: Study protocol, Sap, Icf

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT04563520
Lead sponsor
Emory University
Collaborators
Takeda Pharmaceuticals North America, Inc.
Responsible party
Robert Sidonio (Principal Investigator, Emory University) — Principal investigator
First posted
Sep 24, 2020
Start date
Sep 2026 (estimated)
Primary completion
Mar 2027 (estimated)
Completion
Mar 2027 (estimated)
Last update
Aug 21, 2026

Study contacts

Robert Sidonio, MD
Contact
robert.sidonio.jr@emory.edu
404-785-1637
Robert Sidonio, MD
principal investigator · Emory University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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