SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

NCT ID: NCT04563520

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2027-01-31

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.

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: 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.

FEIBA

Intervention Type: 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.

rFVIIa

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

ACE910, Hemlibra and RO5534262; Activated prothrombin complex (aPCC); Anti-Inhibitor Coagulant Complex; Recombinant activated factor VII

Eligibility Criteria

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

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Robert Sidonio

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Sidonio, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Robert Sidonio, MD

Role: CONTACT

robert.sidonio.jr@emory.edu

404-785-1637

Facility Contacts

Robert Sidonio, MD

Role: primary

robert.sidonio.jr@emory.edu

4047851637

Other Identifiers

2025P010684

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00000804

Identifier Type: -

Identifier Source: org_study_id