Hemophilia APhase 3SAFENCT04563520
SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis
A Phase 3 study testing Emicizumab, FEIBA and rFVIIa in people with Hemophilia A, run by Emory University at 2 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Emicizumab, FEIBA and rFVIIa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2026to Mar 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Emory University Hospital
Atlanta, Georgia, 30322
About this study
Official title: aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)
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.
- Conditions
- Hemophilia A
- Being tested
- Emicizumab, FEIBA, rFVIIa
- Keywords
- hemostatic efficacy, safety, prothrombin complex concentrate
- Medical subject headings
- Hemophilia A, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmicizumabDrug
Also called ACE910, Hemlibra and RO5534262
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.
FEIBADrug
Also called Activated prothrombin complex (aPCC), Anti-Inhibitor Coagulant Complex
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.
rFVIIaDrug
Also called Recombinant activated factor VII
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Emicizumab; Drug: FEIBA; Drug: rFVIIa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and up to 30 minutes after infusion
Secondary outcomes (3)
Number of serious adverse events
Number of serious adverse events will be recorded
Measured: up to 1 year
Number of serious bleeding episodes
Number of serious bleeding episodes will be recorded
Measured: up to 1 year
Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)
Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2020
- Study startSep 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Why it stopped: The study was withdrawn because the pharmaceutical sponsor withdrew support for the study. No participants were enrolled before termination.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Pharmaceuticals North America, Inc.
- Responsible party
- Principal investigator, Robert Sidonio, Emory University
- Investigators
- Robert Sidonio, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04563520
- Sponsor's protocol ID
- STUDY00000804
- Other IDs
- 2025P010684
- Acronym
- SAFE
- Status last verified
- Nov 2026
- First submitted
- 21 Sep 2020
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after de-identification, will be available
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)
- ClinicalTrials.gov ID
- NCT04563520
- Acronym / sponsor ID
- SAFE / STUDY00000804
- Conditions
- Hemophilia A
- Keywords
- hemostatic efficacy, safety, prothrombin complex concentrate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn because the pharmaceutical sponsor withdrew support for the study. No participants were enrolled before termination.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Takeda Pharmaceuticals North America, Inc.
- Study start
- Sep 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 24 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental treatment | Experimental | Drug: Emicizumab, Drug: FEIBA, Drug: rFVIIaParticipants 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. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmicizumabAlso: ACE910, Hemlibra and RO5534262HEMLIBRA® 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. | Drug | Experimental treatment |
| FEIBAAlso: Activated prothrombin complex (aPCC), Anti-Inhibitor Coagulant ComplexFEIBA™ 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. | Drug | Experimental treatment |
| rFVIIaAlso: Recombinant activated factor VIIrFVIIa is a coagulation factor VIIa concentrate indicated for the treatment and control of bleeding episodes occurring in adults and adolescents with hemophilia with inhibitors. | Drug | Experimental treatment |
Primary outcome
Thrombin generation capacity after aPCC (FEIBA) infusion
Time frame: Baseline and up to 30 minutes after 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.
3 secondary outcomes
Number of serious adverse events
Time frame: up to 1 year
Number of serious bleeding episodes
Time frame: up to 1 year
Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)
Time frame: up to 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after de-identification, will be available
Related trials for Hemophilia A
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Sidonio, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Emicizumab, FEIBA and rFVIIa in people with Hemophilia A, run by Emory University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thrombin generation capacity after aPCC (FEIBA) infusion (time frame: Baseline and up to 30 minutes after infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.