Un estudio piloto de la eficacia y seguridad de dupilumab versus placebo en pacientes con síndrome de Netherton (NS-DUPI)
Un estudio piloto aleatorizado, doble ciego, de la eficacia y seguridad de dupilumab versus placebo en pacientes con síndrome de Netherton
To date, there are no effective therapy for the management of Netherton Syndrome (NS) Patients use emollients with a limited efficacy on scaling and no efficacy on skin inflammation and pruritus. They may also use topical corticosteroids or calcineurin inhibitors in case of eczematous lesions. The use of therapies targeting skin inflammation has been reported in a few case reports. Their efficacy is very limited and their uses are limited because of the chronicity of the disease, the impaired skin barrier function and the risk for skin infections and skin cancers. Therefore, there is a huge medical need for novel therapies in NS.The expected consequences of this study are that a 16-week course of dupilumab will be more effective than placebo for the treatment of moderate to severe NS Dupilumab could therefore improve skin condition and quality of life.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a proof of concept (pilot) double-blind randomized placebo-controlled study evaluating the efficacy and safety of dupilumab for the treatment of NS. Patients will be randomized in a 2:1 ratio to receive dupilumab (2 doses of 300 mg), or placebo, at baseline and then 1 dose of dupilumab 300 mg, or placebo, every 2 weeks until week 14 (total of 8 administrations).Moderate to severe NS were selected in order to be able to measure the improvement of skin condition.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Paris, Francia, 75015
- Dermatologie Necker
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Toulouse, Francia
- Dermatology
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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:
- Adult patients affiliated to a social insurance protection regimen.
- Clinical diagnosis of NS (7) (trichorrhexis invaginata, extensive scaling, skin inflammation, allergic manifestations) and absent or marked reduction of LEKTI staining.
- Moderate to severe forms: NASA (Netherton Area Severity Assessment score) score ≥ 5/12 at inclusion.
- Patients able to understand the study procedures including the ability to complete patient-based self-assessment questionnaires.
- Patients who agree to sign the written informed consent.
Exclusion Criteria:
- Hypersensitivity to dupilumab or its excipients.
- Modification of the usual treatment (emollients and topical corticosteroids used on a regular basis) within 2 weeks before inclusion.
- Treatment with topical calcineurin inhibitors 1 week before inclusion.
- Treatment with oral immunosuppressant (including cyclosporine, methotrexate, azathioprine, mycophenolate mofetil), oral retinoids (acitretin, alitretinoin, isotretinoin) or phototherapy within 4 weeks before inclusion.
- Treatment with immunomodulating biologics (Tumor Necrosis Factor (TNF) inhibitor) 16 weeks before inclusion.
- Treatment with another investigational drug within 8 weeks before inclusion.
- Treatment with a systemic antibiotic within 2 weeks before inclusion.
- Active skin infection requiring the use of a systemic therapy within 2 weeks before the inclusion.
- Any other condition that according to the investigator will impair the ability to evaluate treatment effect.
- Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis).
- Current infections including infection with helminthes.
- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing age, potentially sexually active, and unwilling to use adequate birth control methods.
- Mental or physical incapacity to fill in the questionnaires.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Dupilumab
The patient will receive 2 doses at baseline and then 1 dose every 2 weeks (8 administrations in total) of Dupilumab 300 mg (syringe of 2 mL for subcutaneous administration). |
administration of dupilumab corresponding to dupilumab arm |
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Comparador de placebos: Placebo
The patient will receive 2 doses at baseline and then 1 dose every 2 weeks (8 administrations in total) of placebo (syringe of 2 mL for subcutaneous administration).. |
administration of placebo corresponding to placebo arm |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The severity of the disease of the Netherton Area Severity Assessment score (NASA).
Periodo de tiempo: Day 0 and week 16
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NASA score |
Day 0 and week 16
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Clinical efficacy severity of pruritus and pain
Periodo de tiempo: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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NASA score |
Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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Presence of infections (adverse event)
Periodo de tiempo: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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Number of Bacterial or viral Skin infections |
Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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Quantity of dermocorticosteroids used between each visit will be evaluated by questioning the patient.
Periodo de tiempo: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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number of tubes multiplied by the weight of one tube |
Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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QOL score
Periodo de tiempo: Day 0, Week 16 and 28
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QOL score |
Day 0, Week 16 and 28
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Skin inflammation
Periodo de tiempo: Day 0 and week 16
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number of inflammation markers on biopsies |
Day 0 and week 16
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Protease activity
Periodo de tiempo: Day 0 and week 16
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number of protease markers on biopsies |
Day 0 and week 16
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Microbiome qualitative and quantitative analysis
Periodo de tiempo: Day 0 and week 16
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number and form of bacteria |
Day 0 and week 16
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Transepidermal water loss (TEWL)
Periodo de tiempo: Day 0 and Week 16
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Measured by a Tewameter applied on a standardized area in the anterior aspect of the forearm, |
Day 0 and Week 16
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Safety of dupilumab
Periodo de tiempo: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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Blood tests performed every month until Week 16 (liver and renal tests, total blood count) |
Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Juliette MAZEREEUW-HAUTIER, Toulouse Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
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
- Infantil, Recién Nacido, Enfermedades
- Enfermedades de la piel
- Anomalías congénitas
- Anomalías Múltiples
- Enfermedades De La Piel Genéticas
- Anomalías de la piel
- Queratosis
- Eritrodermia Ictiosiforme Congénita
- Ictiosis
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades de la piel y del tejido conectivo
- Síndrome de Netherton
Otros números de identificación del estudio
- RC31/19/0045
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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