Clinical trial NCT04563520: SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemophilia A
Keywords: hemostatic efficacy
safety
prothrombin complex concentrate
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2020-09-24
Enrollment: 5
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Thrombin generation capacity after aPCC (FEIBA) infusion
timeFrame: Baseline and up to 30 minutes after infusion
Secondary outcomes:
measure: Number of serious adverse events
timeFrame: up to 1 year
measure: Number of serious bleeding episodes
timeFrame: up to 1 year
measure: Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Robert Sidonio, MD
role: PRINCIPAL_INVESTIGATOR
References: