Resumen

La dermatitis atópica (DA) es una afección cutánea que puede causar erupción cutánea y prurito debido a la inflamación de la piel. Las terapias tópicas aplicadas sobre la piel pueden no ser suficientes para controlar la DA en participantes que requieren tratamiento sistémico antiinflamatorio. Este estudio compara upadacitinib con dupilumab en participantes pediátricos con DA moderada a grave que son candidatos a terapia sistémica. Se evaluarán los eventos adversos y los cambios en la actividad de la enfermedad. Upadacitinib es un fármaco aprobado para el tratamiento de pacientes con DA a partir de los 12 años. Los participantes recibirán upadacitinib (en dosis diaria) o dupilumab (en la dosis indicada en la ficha técnica, cada 2 o 4 semanas). Los participantes se estratificarán según la gravedad de la enfermedad, la edad y la respuesta al tratamiento previo. Existe 1 probabilidad entre 5 de que los participantes reciban dupilumab durante la cohorte aleatorizada. Se estima la incorporación de aproximadamente 675 participantes de entre 2 y menos de 12 años de edad en aproximadamente 150 centros a nivel mundial. La población del estudio (definida según la edad de los participantes o el tratamiento previo) a incluir depende de los requisitos regulatorios locales y/o de los acuerdos correspondientes. Los participantes recibirán comprimidos orales de upadacitinib una vez al día (o solución oral dos veces al día) durante 160 semanas, o dupilumab según su ficha técnica durante 52 semanas, con seguimiento durante 30 días tras la última dosis de upadacitinib y al menos 12 semanas tras la última dosis de dupilumab. Es posible que la carga del tratamiento en este ensayo sea mayor en comparación con el tratamiento estándar. Los participantes asistirán a visitas periódicas durante el estudio en un hospital o clínica. El efecto del tratamiento se verificará mediante evaluaciones clínicas, análisis de sangre, monitoreo de efectos secundarios y cumplimentación de cuestionarios.

Elegibilidad

Edad mínima: 2 YearsEdad máxima: 11 YearsSexo: ALL

Criterios de inclusión

A minimum weight of 10 kg and weight and height \> 5th percentile for their age according to local standard growth charts at the Baseline Visit.
Atopic Dermatitis (AD), according to Hanifin and Rajka criteria, with onset of symptoms at least 6 months prior to Baseline.
Eczema Area and Severity Index (EASI) score \>= 16; vIGA-AD score \>= 3 (Note: In countries where dupilumab is only approved for severe AD, subjects to be included in the Randomized Cohort should have severe AD \[vIGA-AD = 4\]); \>= 10% Body Surface Area of AD involvement at the Baseline Visit; and Baseline weekly average of daily Worst Itch Scale (WIS) or Worst Scratch/Itch numerical rating scale (WSI-NRS) \>= 4.
Participant must satisfy at least one of the following criteria (Note: More than 1 criterion may apply to an individual participant. All applicable criteria for each individual participant should be reported):
To be included in the Randomized Cohort (Note: Participants must have severe AD \[vIGA-AD = 4\] in countries where dupilumab is approved only for severe AD.):
\[For all countries except US\] Documented history of inadequate response or intolerance to TCS and/or TCI OR for whom use of one or more of these topical treatments is medically inadvisable (e.g., high disease burden, Scoring Atopic Dermatitis (SCORAD) \> 50, EASI score \> 21, or vIGA-AD \> 3).
For dupilumab-naïve participants: History of inadequate response to a systemic therapy for AD other than dupilumab or oral corticosteroids or for whom the available systemic treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
History of inadequate response to 2 or more courses of oral corticosteroid therapy given for \>= 14 days within 6 months prior to Screening or history of oral corticosteroid rebound, defined as recurrence of AD symptoms within 4 months after its discontinuation.
For dupilumab-exposed participants: Prior exposure to dupilumab without documented history of inadequate response or intolerance (i.e., discontinuation of dupilumab for a non-medical reason, such as, but not limited to, non-coverage or loss of coverage for the drug by health insurance, or other logistic challenges \[not safety- or efficacy-related\] precluding the participants continued access to dupilumab).
To be included in the Dupi-IR/Dupi-Medically Inadvisable Cohort:
Previous inadequate response or intolerance to dupilumab OR
Dupilumab is medically inadvisable (e.g., allergy to a component of dupilumab, etc.) AND a documented history of inadequate response or intolerance to TCS and/or TCI.

Criterios de exclusión

Known history of retinal detachment, previous cataract surgery, previous significant ocular trauma, or a known congenital ocular abnormality.
For Randomized Cohort: diagnosed active parasitic infection; suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.
Current or past history of other active skin diseases (e.g., psoriasis or Netherton syndrome or lupus erythematosus) or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or which would interfere with the appropriate assessment of AD lesions.
Have used topical treatments for AD (except for topical emollient treatments) including but not limited to TCS, TCI, or topical phosphodiesterase type 4 (PDE-4) inhibitors, within 7 days of the Baseline Visit or any the following prohibited concomitant AD treatments within the specified timeframes below prior to the Baseline Visit:
Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, PDE-4 inhibitors, interferon-γ, and mycophenolate mofetil within 4 weeks;
Dupilumab within 8 weeks;
Targeted biologic treatments (other than dupilumab) within 5 half-lives (if known) or within 12 weeks, whichever is longer;
Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks.

Ubicaciones

Sanatorio 9 de Julio /ID# 267678

San Miguel de Tucumán, Tucumán Province, Argentina

RECRUITING

Conexa Investigacion Clinica /ID# 268728

Buenos Aires, Argentina

RECRUITING

Instituto de Neumonología y Dermatología /ID# 266146

Buenos Aires, Argentina

RECRUITING

Psoriahue - Buenos Aires /ID# 267737

Buenos Aires, Argentina

RECRUITING

Estudio de fase 3, abierto, con evaluadores de eficacia enmascarados, que compara la seguridad y eficacia de upadacitinib frente a dupilumab en niños de 2 a menos de 12 años de edad con dermatitis atópica moderada a grave

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Upadacitinib

Dupilumab

Ubicaciones

Sanatorio 9 de Julio /ID# 267678

Conexa Investigacion Clinica /ID# 268728

Instituto de Neumonología y Dermatología /ID# 266146

Psoriahue - Buenos Aires /ID# 267737

Patrocinadores

Contactos

ABBVIE CALL CENTER