Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 2)

Study Overview
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Brief Summary
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Multicenter, phase III, randomized, blinded, controlled, parallel group.

Detailed Description
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This is a 24-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period to evaluate the efficacy and safety of LYR-210 compared with sham control for treatment in adults with CRS.

Official Title
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ENLIGHTEN 2: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults

Conditions
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Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)

Intervention / Treatment
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* Drug: LYR-210
* Drug: Sham procedure control
* Other: Background therapy


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Inability to tolerate topical anesthesia 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYR-210<br>Single administration of LYR-210 drug matrix (7500 μg) | Drug: LYR-210<br>* LYR-210 drug matrix (mometasone furoate)<br>Other: Background therapy<br>* Daily Saline Irrigation<br>|
| Sham Comparator: Sham procedure control<br>Single mock administration procedure | Drug: Sham procedure control<br>* Sham procedure control<br>Other: Background therapy<br>* Daily Saline Irrigation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CFBL in the 7-day average composite score of 3CS at Week 24. | 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. | 24 Weeks | 
| CFBL in the 7-day average CS score of nasal blockage/obstruction/congestion at Week 24. | 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. | 24 Weeks | 
| CFBL in the 7-day average CS score of anterior/posterior nasal discharge at Week 24. | 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. | 24 Weeks | 
| CFBL in the 7-day average CS score of facial pain/pressure at Week 24. | 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. | 24 Weeks | 
| CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) total score at Week 24. | 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. | 24 Weeks | 
| CFBL in the 3-D volumetric CT score at Week 20. |  | 20 Weeks | 
| Number and percent of participants requiring rescue treatment through Week 24 |  | 24 Weeks |