E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Rhinosinusitis (CRS) in Adults |
Rinosinusitis Crónica (RSC) en Adultos |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Rhinosinusitis (CRS) in Adults |
Rinosinusitis Crónica (RSC) en Adultos |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009137 |
E.1.2 | Term | Chronic sinusitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the efficacy of LYR-210, compared with a sham procedure control, in improving the 3 cardinal symptoms of CRS in CRS participants without nasal polyps who had previously failed medical management. |
El objetivo primario es evaluar la eficacia de LYR-210, comparado con un procedimiento simulado de control, en mejorar los tres síntomas cardinales de RSC en participantes con RSC sin pólipos nasales que hayan fallado previamente en el manejo médico |
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E.2.2 | Secondary objectives of the trial |
Evaluate the efficacy of LYR-210, compared with sham control, in improving the 3 cardinal symptoms of CRS in CRS participants without nasal polyps or with nasal polyps of grade 1 who had previously failed medical management.
Evaluate the efficacy of LYR-210, compared with sham control, in improving CRS related quality of life, CRS symptoms, the extent of inflammation in the ethmoid sinuses, and the need for rescue treatment in surgery naïve CRS participants without nasal polyps or who had previously failed medical management. |
Evaluar la eficacia de LYR-210, comparado con un procedimiento simulado de control, en mejorar los tres síntomas cardinales de RSC en participantes con RSC sin pólipos nasales o con pólipos nasales de grado 1 que hayan fallado previamente en el manejo médico.
Evaluar la eficacia de LYR-210, comparado con un procedimiento simulado de control, en mejorar la calidad de vida relacionada con RSC, los síntomas de RSC, la extensión de la inflamación en los senos etmoidales, y la necesidad de tratamiento de rescate en participantes con RSC que no se hayan sometido a cirugía y que no presenten pólipos nasales o que hayan tenido un fracaso previo en el manejo médico. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥18 - Diagnosed as having CRS - Bilateral ethmoid disease confirmed on computed tomography (CT) - Mean 3 cardinal symptom (3CS) score - Undergone at least 2 trials of medical treatments in the past - Has been informed of the nature of the study and provided written informed consent - Agrees to comply with all study requirements - Willing to cancel or be removed from waitlist for any preplanned elective sinonasal surgery for the duration of the study |
-Mayor de 18 años -Diagnóstico de RSC -Enfermedad etmoidea bilateral confirmada por tomagrafía computerizada (CT) -Puntuación media de 3 síntomas cardinales (3SC) -Haber recibido al menos dos tratamientos médicos de prueba en el pasado -Ha sido informado de la naturaleza del estudio y ha otorgado su consentimiento informado por escrito -Se compromete a cumplir todos los requisitos del estudio -Debe aceptar cancelar o salir de la lista de espera de cualquier cirugía sinonasal prevista/programada durante la duración del estudio |
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E.4 | Principal exclusion criteria |
- Inability to tolerate topical anesthesia - Previous nasal surgery or polypectomy within 3 months of screening - Presence of nasal polyp grade 2 or higher - Seasonal allergic rhinitis - Perennial rhinitis with symptoms that are well controlled by regular use of intranasal corticosteroids - Severe asthma - Obstruction preventing proper placement and retention of LYR-210 as seen on endoscopy and CT - History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, atrophic rhinitis, or odontogenic sinusitis - Anatomic variation that, in the opinion of the investigator, would adversely impact placement of LYR-210 as seen on CT - Known history of hypersensitivity or intolerance to corticosteroids Known history of hypothalamic pituitary adrenal axial dysfunction - Previous pituitary or adrenal surgery - Dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. - Past or present acute or chronic intracranial or orbital complications of CRS - History or diagnosis (in either eye) of glaucoma or ocular hypertension - Past or present functional vision in 1 or both eyes - Past, present, or planned organ transplant or chemotherapy with immunosuppression - Currently positive for COVID-19 or residual sinonasal symptoms from a previous COVID-19 infection - Pregnant or breast feeding. Females of child-bearing potential must test negative for pregnancy at the time of screening - Evidence of disease or condition expected to compromise survival or ability to complete follow-up assessments - Currently participating in an investigational drug or device study - Determined by the investigator as not suitable to be enrolled |
-Incapacidad para tolerar la anestesia tópica -Cirugía nasal o polipectomía previa en los tres meses anteriores a la visita de selección. -Presencia de pólipos nasales de grado 2 o superior. -Rinitis alérgica estacional. -Rinitis perenne con síntomas bien controlados con el uso regular de corticoides intranasales. -Asma grave. -Obstrucción que impida la correcta colocación y retención de LYR 210 según lo observado en la endoscopia o CT. -Antecedentes o signos clínicos o sospecha de sinusitis fúngica invasora, rinosinusitis fúngica alérgica, rinitis atrófica o sinusitis odontogénica. -Variación anatómica que, en opinión del investigador, afectaría negativamente a la colocación de LYR-210 según lo observado en el TAC. -Antecedentes conocidos de hipersensibilidad o intolerancia a los corticoides. -Antecedentes conocidos de disfunción del eje hipotálamo-hipófiso-suprarrenal. -Cirugía hipofisaria o suprarrenal previa. -Procedimiento/implante dental en la dentadura maxilar en las cuatro semanas previas a la visita de selección. -Complicaciones intracraneales u orbitarias, agudas o crónicas, pasadas o presentes de la RSC. -Antecedentes o diagnóstico (en cualquier ojo) de glaucoma o hipertensión ocular. -Pérdida de visión funcional de uno o ambos ojos. -Trasplante de órgano pasado, actual o programado o quimioterapia con inmunodepresión. -Positividad actual para COVID-19 o síntomas sinonasales residuales de una infección previa por COVID-19. -Embarazo o lactancia. Las mujeres en edad fértil deberán dar negativo en una prueba de embarazo en suero en el momento de la selección. -Signos de enfermedad o trastorno que previsiblemente comprometerá la supervivencia o la capacidad de realizar las evaluaciones de seguimiento. -Participación actual en otro estudio con un fármaco o producto. -El investigador determina que el paciente no es apto para ser incluido. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline (CFBL) in the 7-day average composite score of the 3 cardinal symptoms (3CS) of nasal blockage/obstruction/congestion, facial pain/pressure, and anterior/posterior nasal discharge at Week 24 in participant without nasal polyps. |
El criterio de valoración prinicipal es la variación entre el momento basal y la semana 24 de la puntuación combinada media de 7 días de los tres síntomas cardinales (3SC): obstrucción/congestión nasal, secreción nasal anterior/posterior y dolor/presión facial en los participantes sin pólipos nasales. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.CFBL in the 7-day average composite score of 3CS at Week 24 2.CFBL in the 7-day average CS score of nasal blockage/obstruction/congestion at Week 24 3.CFBL in the 7-day average CS score of anterior/posterior nasal discharge at Week 24 4.CFBL in the 7-day average CS score of facial pain/pressure at Week 24 5.CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) total score at Week 24 6.Rescue treatment through Week 24 7.CFBL in the 3-D volumetric CT analysis at Week 20 |
1.Variación entre el momento basal y la semana 24 de la puntuación combinada media de 7 días de los 3SC. 2.Variación entre el momento basal y la semana 24 de la puntuación media de 7 días del SC de obstrucción/congestión nasal. 3.Variación entre el momento basal y la semana 24 de la puntuación media de 7 días del SC de secreción nasal anterior/posterior. 4.Variación entre el momento basal y la semana 24 de la puntuación media de 7 días del SC de dolor/presión facial. 5.Variación entre el momento basal y la semana 24 de la puntuación total SNOT-22 (Prueba de resultados nasosinusales de 22 apartados). 6.Necesidad de tratamiento de rescate hasta la semana 24. 7.Variación entre el momento basal y la semana 20 del porcentaje de opacificación bilateral de los senos etmoidales anterior y posterior, determinada mediante TAC volumétrica 3 D. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Procedimiento simulado |
Sham procedure |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study (EOS) is defined as the date of the last EOS visit of the last participant of the study. |
El fin del estudio se define como la fecha de la visita de fin de estudio del último participante del estudio |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |