Un estudio para probar un medicamento (fitusiran) para prevenir hemorragias en personas con hemofilia grave que previamente recibieron tratamiento preventivo con emicizumab
Un estudio de tratamiento abierto de un solo grupo para investigar la seguridad y tolerabilidad del cambio de profilaxis con emicizumab a fitusiran en participantes masculinos ≥18 años con hemofilia A grave, con o sin inhibidores
This is an exploratory, single group, Phase 4, study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.
This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥12 years, who were previously receiving emicizumab prophylaxis.
Study details include:
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The study duration will be up to approximately 28 months:
- There will be an approximately 2-month screening period.
- There will be an approximately 2-month period before fitusiran treatment starts (pre-fitusiran treatment period)
- The fitusiran treatment duration will be up to 18-months (fitusiran treatment period)
- The antithrombin (AT) follow-up (FU) period will be approximately 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%).
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The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.
Descripción general del estudio
Estado
Condiciones
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Trial Transparency email recommended (Toll free for US & Canada)
- Número de teléfono: option 6 800-633-1610
- Correo electrónico: Contact-US@sanofi.com
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90027
- Reclutamiento
- Children's Hospital Los Angeles- Site Number : 8400005
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Mississippi
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Flowood, Mississippi, Estados Unidos, 39232
- Reclutamiento
- Southern Specialty Research- Site Number : 8400011
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Taipei, Taiwán, 100
- Reclutamiento
- Investigational Site Number : 1580001
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Male participants must be ≥12 years of age inclusive, at the time of signing the informed consent
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Diagnosis of severe congenital hemophilia A (FVIII < 1%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
- Inhibitor titer of ≥0.6 BU/mL at Screening, or
- Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, or
- Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of anamnestic response.
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Participants who are currently on the full labeled dose of emicizumab prophylaxis, irrespective of inhibitor/non-inhibitor status.
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Signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Known coexisting bleeding disorders
- History of antiphospholipid antibody syndrome.
- History of arterial or venous thromboembolism, atrial fibrillation, significant valvular disease, myocardial infarction, angina, transient ischemic attack, or stroke. Participants who have experienced thrombosis associated with indwelling venous access may be enrolled.
- Presence of clinically significant liver disease
- Current or prior participation in a fitusiran trial
- Current or prior participation in a gene therapy trial
- AT activity <60% at Screening, as determined by central laboratory measurement
- Coexisting thrombophilic disorder - Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
- Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
- Presence of acute or chronic hepatitis B infection
- Known to be HIV positive with CD4 count <200 cells/μL.
- Reduced renal function
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: fitusiran
The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1. Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18. Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement. AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement. |
Pharmaceutical form:Solution for injection-Route of administration:Subcutaneous (SC) injection
Otros nombres:
Pharmaceutical form: Solution for injection-Route of administration: Intravenous (IV) injection Pharmaceutical form:Solution for injection-Route of administration:Intravenous (IV) injection Pharmaceutical form:Solution for injection-Route of administration:SC injection |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of participants with Adverse events (AEs) during the fitusiran treatment
Periodo de tiempo: From Day 1 up to Month 4
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Incidence, severity, and seriousness, of AEs occurred during fitusiran treatment period will be reported |
From Day 1 up to Month 4
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The peak thrombin generation (TG) - pre fitusiran treatment
Periodo de tiempo: From Month -2 up to Day 1
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Central laboratory assessments (peak TG) will be reported for pre-fitusiran period |
From Month -2 up to Day 1
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The peak TG during fitusiran treatment
Periodo de tiempo: From Day 1 up to Month 4
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Central laboratory assessments (peak TG) will be reported for fitusiran treatment period |
From Day 1 up to Month 4
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The antithrombin (AT) levels during pre-fitusiran treatment
Periodo de tiempo: From Month -2 up to Day 1
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Central laboratory assessments (AT) will be reported for pre-fitusiran treatment period |
From Month -2 up to Day 1
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The AT levels during fitusiran prophylaxis
Periodo de tiempo: From Day 1 up to Month 4
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Central laboratory assessments (AT) will be reported for fitusiran treatment |
From Day 1 up to Month 4
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Emicizumab concentrations in plasma
Periodo de tiempo: Up to Month 4 of fitusiran treatment
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Emicizumab concentrations in plasma will be reported |
Up to Month 4 of fitusiran treatment
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Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment
Periodo de tiempo: From Day 1 up to Month 18
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Incidence, severity, and seriousness of AEs will be reported |
From Day 1 up to Month 18
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Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores
Periodo de tiempo: From approximately Month -2 to Month 19 [end of study (EoS) visit]
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The three domains of effectiveness, convenience, and global satisfaction will be reported |
From approximately Month -2 to Month 19 [end of study (EoS) visit]
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Participants' treatment preferences (via the Preference Questionnaire)
Periodo de tiempo: At Month 12
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The Preference questionnaire Data will be reported |
At Month 12
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Change in adult participants' pain intensity during the fitusiran treatment period over time
Periodo de tiempo: From approximately Month - 2 to Month 19 (EoS) visit
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The PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Intensity 3a v2.0 consists of three items measuring the worst, average, and current intensity of pain with a recall period of 7 days. Each question has five response options ranging from one ('no pain') to five ('very severe'). Adult participants (age ≥ 18 years) will self-complete the PROMIS Pain Intensity 3a v2.0 questionnaire. |
From approximately Month - 2 to Month 19 (EoS) visit
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Change in adolescent participants' pain intensity during the fitusiran treatment period over time
Periodo de tiempo: From approximately Month - 2 to Month 19 (EoS) visit
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The PROMIS Pediatric Numeric Rating Scale v.1.0 - Pain Intensity 1a consists of one item measuring the average intensity of pain with a recall period of 7 days. The question has ten response options ranging from one ('no pain') to ten ('worst pain'). Adolescent participants (age ≥12 years and <17 years) will self-complete the PROMIS Pediatric Pain Intensity 1a v.1.0. |
From approximately Month - 2 to Month 19 (EoS) visit
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Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time
Periodo de tiempo: From approximately Month - 2 to Month 19 (EoS) visit
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Participants' physical functioning and physical activity data during the fitusiran treatment period will be collected via the International Physical Activity Questionnaire and reported |
From approximately Month - 2 to Month 19 (EoS) visit
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Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time
Periodo de tiempo: From approximately Month - 2 to Month 19 (EoS) visit
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HJHS during the fitusiran treatment period will be reported |
From approximately Month - 2 to Month 19 (EoS) visit
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Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis
Periodo de tiempo: From Month 4 up to Month 18 (14-month extension period)
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The frequency of treated bleeding episodes will be reported |
From Month 4 up to Month 18 (14-month extension period)
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Clinical Sciences & Operations, Sanofi
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades Genéticas Congénitas
- Enfermedades hematológicas
- Trastornos de la coagulación de la sangre
- Trastornos hemorrágicos
- Trastornos de la coagulación de la sangre, hereditarios
- Trastornos de proteínas de coagulación
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades hemic y linfáticas
- Hemofilia A
- emicizumab
- Fitusiran
Otros números de identificación del estudio
- SFY17741
- 2022-502414-84 (Identificador de registro: CTIS)
- U1111-1280-7227 (Identificador de registro: ICTRP)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Información sobre medicamentos y dispositivos, documentos del estudio
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