Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 1)

ENLIGHTEN 1: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis (CRS) in Adults

Multicenter, phase III, randomized, blinded, controlled, parallel group with safety extension phase with crossover or continued treatment.

This is a 52-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period followed by a safety extension phase with crossover or continued treatment to evaluate the efficacy and safety of LYR-210 compared with sham control for treatment in adults with CRS.

Change from baseline (CFBL) in the 7-day average composite score of 3 cardinal symptoms (3CS) in participants without nasal polyps.

The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores.

Nasal blockage/obstruction/congestion is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms.

Anterior/posterior nasal discharge is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms.

Facial pain/pressure is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms.

The SNOT-22 questionnaire is a 22-item disease-specific quality of life instrument. Each symptom is scored on a 6-point scale where 0 = no problem and 5 = problem as bad as it can be. The total SNOT-22 score is the sum of the 22 items and can range from 0 to 110 with higher scores indicating worse symptoms.

Inclusion Criteria: Age ≥18 Diagnosed as having CRS Undergone at least 2 trials of medical treatments in the past Mean 3 cardinal symptom (3CS) score Bilateral ethmoid disease confirmed on CT Has been informed of the nature of the study and provided written informed consent Agrees to comply with all study requirements If on a waiting list for sinonasal surgery, willing to be removed from list or have surgery date cancelled for the duration of the study. Exclusion Criteria: Inability to tolerate topical anesthesia or endoscopic procedure Previous nasal surgery 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 History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, atrophic rhinitis, or odontogenic sinusitis Obstruction preventing proper placement and retention of LYR-210 as seen on endoscopy 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 only 1 eye 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