SAFE-onderzoek: veiligheid van aPCC na profylaxe met emicizumab (SAFE)
aPCC- en emicizumab-veiligheidsonderzoek bij congenitale hemofilie A-patiënten met remmers (SAFE-onderzoek: veiligheid van aPCC na profylaxe met emicizumab)
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Fase
- Fase 3
Contacten en locaties
Studie Locaties
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory University Hospital
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Atlanta, Georgia, Verenigde Staten, 30322
- Children's Healthcare of Atlanta
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: 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. |
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.
Andere namen:
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.
Andere namen:
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.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Thrombin generation capacity after aPCC (FEIBA) infusion
Tijdsspanne: Baseline and up to 30 minutes after infusion
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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. |
Baseline and up to 30 minutes after infusion
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Number of serious adverse events
Tijdsspanne: up to 1 year
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Number of serious adverse events will be recorded |
up to 1 year
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Number of serious bleeding episodes
Tijdsspanne: up to 1 year
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Number of serious bleeding episodes will be recorded |
up to 1 year
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Number of episodes of thrombotic events including thrombotic microangiopathy (TMA)
Tijdsspanne: up to 1 year
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Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded |
up to 1 year
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Robert Sidonio, MD, Emory University
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Genetische ziekten, aangeboren
- Hematologische ziekten
- Bloedstollingsstoornissen
- Hemorragische aandoeningen
- Genetische ziekten, X-gekoppeld
- Bloedstollingsstoornissen, geërfd
- Coagulatie-eiwitstoornissen
- Aangeboren, erfelijke en neonatale ziekten en afwijkingen
- Hemische en lymfatische ziekten
- Hemofilie A
- Hemofilie B
- emicizumab
- recombinant FVIIA
- anti-remmer coagulant complex
Andere studie-ID-nummers
- STUDY00000804
- 2025P010684 (Andere identificatie: Emory Insight Humans IRB)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
All of the individual participant data collected during the trial, after de-identification, will be available
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
- ICF
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
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