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

Primary Purpose

Hemophilia A

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

aPCC-emicizumab

FEIBA

rFVIIa

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring hemostatic efficacy, safety, prothrombin complex concentrate

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Healthcare of AtlantaRecruiting
Emory University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental treatment

Arm Description

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. If there is less than a "good' response in bleed event response efficacy as stated above at 48 hours or less than "moderate" for surgical event control, the local PI can consider the use of thrombin generation guided rFVIIa with max dose no more than 90 µg/kg/dose every 8 hours for 72 hours, with wean to occur for no more than 7 total days without further discussion with the PI.

Outcomes

Primary Outcome Measures

Number of serious adverse events

Number of serious adverse events will be recorded

Number of serious bleeding episodes

Number of serious bleeding episodes will be recorded

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

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

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT04563520

First Posted

September 21, 2020

Last Updated

October 5, 2023

Sponsor

Emory University

Collaborators

Takeda Pharmaceuticals North America, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04563520

Brief Title

SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

Acronym

SAFE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 2023 (Anticipated)

Primary Completion Date

September 2025 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Takeda Pharmaceuticals North America, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A

Keywords

hemostatic efficacy, safety, prothrombin complex concentrate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

aPCC-emicizumab

Other Intervention Name(s)

ACE910, Hemlibra and RO5534262

Intervention Description

Intervention Type

Drug

Intervention Name(s)

FEIBA

Other Intervention Name(s)

Anti-Inhibitor Coagulant Complex

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

rFVIIa

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of serious adverse events

Description

Number of serious adverse events will be recorded

Time Frame

up to 2 years

Title

Number of serious bleeding episodes

Description

Number of serious bleeding episodes will be recorded

Time Frame

up to 2 years

Title

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

Description

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

Time Frame

up to 2 years

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Robert Sidonio, MD

Phone

404-785-1637

robert.sidonio.jr@emory.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Sidonio, MD

Organizational Affiliation

Emory University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Healthcare of Atlanta

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Robert Sidonio, MD

Phone

404-785-1637

robert.sidonio.jr@emory.edu

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All of the individual participant data collected during the trial, after de-identification, will be available

Learn more about this trial

SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis

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