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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
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

First Posted
September 21, 2020
Last Updated
October 5, 2023
Sponsor
Emory University
Collaborators
Takeda Pharmaceuticals North America, Inc.
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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
No
Product Manufactured in and Exported from the U.S.
No
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
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.
Intervention Type
Drug
Intervention Name(s)
aPCC-emicizumab
Other Intervention Name(s)
ACE910, Hemlibra and RO5534262
Intervention 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.
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
No
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
Email
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
Email
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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