Resumen

Objetivo primario: Evaluar la eficacia de dupilumab según la reducción en la semana 24 de la opacificación sinusal en tomografía computarizada (TC) en el grupo de dupilumab únicamente. Objetivos secundarios: * Evaluar la eficacia de dupilumab según la reducción en la semana 24 de la opacificación sinusal en TC y la puntuación total de síntomas sinusales (sTSS) en comparación con placebo. * Evaluar la seguridad y tolerabilidad de dupilumab en pacientes con RSCsPN en comparación con placebo. * Evaluar la farmacocinética (PK) de dupilumab en pacientes con RSCsPN en comparación con placebo. * Evaluación de la inmunogenicidad de dupilumab a lo largo del tiempo en comparación con placebo.

Descripción detallada

La duración del estudio para cada participante incluirá un período de selección de 2 a 4 semanas, un período de intervención con producto en investigación (IMP) aleatorizado de 24 a 52 semanas y un período de seguimiento de 12 semanas.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Participant must be at least 18 years of age at the time of signing the informed consent form (ICF).
Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK ≥8 and bilateral ethmoid opacification before randomization.
Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit 1.
Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of ≥ 2 at Visit 1 (day score) and Visit 2 (weekly average score).
Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).
Participants must have one of the 2 following features:
Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS,
Treatment with systemic corticosteroids (SCS) therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS.

Criterios de exclusión

Participants with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy
Nasal cavity malignant tumor and benign tumors.
Forced expiratory volume (FEV1) ≤50% of predicted normal at Visit 1.
Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis.
Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect participation in the study
Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
Known or suspected immunodeficiency
History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.
History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.
Participants in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event.
Participants who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.
Participants on unstable dose of intranasal corticosteroids (INCS) spray 4 weeks prior to Screening Visit (Visit1) and during screening period.
Participants who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.
Participants who have taken:
Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
Any investigational mAb within 5 half-lives prior to Visit 1
Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1.
Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
Leukotriene antagonists/modifiers unless participant is on a continuous treatment for at least 30 days prior to Visit 1.
Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period.
Participants received SCS during screening period (between Visit 1 and Visit 2).
Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Estudio aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia y seguridad de dupilumab en pacientes con rinosinusitis crónica no controlada sin poliposis nasal (RSCsPN)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dupilumab SAR231893

Placebo

Ubicaciones

Investigational Site Number : 0320002

Investigational Site Number : 0320003

Investigational Site Number : 0320001

Patrocinadores