Studio SAFE: sicurezza dell'aPCC dopo la profilassi con emicizumab (SAFE)
Studio sulla sicurezza di aPCC ed emicizumab nei pazienti con emofilia congenita A con inibitori (studio SAFE: sicurezza di aPCC dopo la profilassi con 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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Georgia
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Atlanta, Georgia, Stati Uniti, 30322
- Emory University Hospital
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Atlanta, Georgia, Stati Uniti, 30322
- Children's Healthcare of Atlanta
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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.
Altri nomi:
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.
Altri nomi:
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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Thrombin generation capacity after aPCC (FEIBA) infusion
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of serious adverse events
Lasso di tempo: up to 1 year
|
Number of serious adverse events will be recorded |
up to 1 year
|
|
Number of serious bleeding episodes
Lasso di tempo: up to 1 year
|
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)
Lasso di tempo: up to 1 year
|
Number of episodes of thrombotic events including thrombotic microangiopathy (TMA) will be recorded |
up to 1 year
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Robert Sidonio, MD, Emory University
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie genetiche, congenite
- Malattie ematologiche
- Disturbi della coagulazione del sangue
- Disturbi emorragici
- Malattie genetiche, legate all'X
- Disturbi della coagulazione del sangue, ereditari
- Disturbi delle proteine della coagulazione
- Malattie e anomalie congenite, ereditarie e neonatali
- Malattie emiche e linfatiche
- Emofilia A
- Emofilia B
- emicizumab
- FVIIA ricombinante
- complesso coagulante anti-inibitore
Altri numeri di identificazione dello studio
- STUDY00000804
- 2025P010684 (Altro identificatore: Emory Insight Humans IRB)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
All of the individual participant data collected during the trial, after de-identification, will be available
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
prodotto fabbricato ed esportato dagli Stati Uniti
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