LYR-210 Depot (LYR-210) for Adult Subjects With Chronic Sinusitis (LANTERN Study)

Study Overview
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Brief Summary
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This is a Phase II, Randomized, Blinded, Sham Procedure-Controlled, Parallel-Group Trial to Evaluate the Efficacy, Safety and Tolerability of LYR-210 in Adult Subjects with Chronic Sinusitis.

Detailed Description
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LYR-210 is a drug depot, which contains the anti-inflammatory medication mometasone furoate (MF) pre-loaded in a single use applicator. LYR-210 is intended to be placed bilaterally into the sino-nasal passages by an otolaryngologist. Once in place, each LYR-210 drug depot is designed to gradually deliver sustained topical doses of MF to the inflamed mucosal sinus tissue over 24 weeks.

Official Title
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A Phase II, Randomized, Blinded, Sham Procedure-Controlled, Parallel-Group Trial to Evaluate the Efficacy, Safety and Tolerability of LYR-210 in Adult Subjects With Chronic Sinusitis (LANTERN Study)

Conditions
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Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)

Intervention / Treatment
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* Drug: LYR-210
* Other: Sham comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CS. Two trials of medical treatments for CS in the past. Minimum CS symptom score. Ability to tolerate topical anesthesia. Has been informed of the nature of the study and has provided written informed consent as approved by the Institutional Review Board (IRB)/Ethics Committee (EC) of the respective clinical site. Agrees to comply with all study requirements. Exclusion Criteria: Have undergone previous sinus surgery. Pregnant or breast feeding. Known history of hypersensitivity or intolerance to corticosteroids. History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, or atrophic rhinitis. Known history of hypothalamic pituitary adrenal axial dysfunction or having a morning serum cortisol level at screening outside of the normal range. Had dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. Past or present functional vision in only one eye. Has cataracts Past, present, or planned organ transplant or chemotherapy with immunosuppression. Currently participating in an investigational drug or device study

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYR-210 (Low Dose)<br>In-office bilateral placement of the LYR-210 drug depot (mometasone furoate low dose) in the middle meatus | Drug: LYR-210<br>* A single administration of LYR-210 depot<br>|
| Experimental: LYR-210 (High Dose)<br>In-office bilateral placement of the LYR-210 drug depot (mometasone furoate high dose) in the middle meatus | Drug: LYR-210<br>* A single administration of LYR-210 depot<br>|
| Sham Comparator: Sham Procedure<br>In-office bilateral sham procedure | Other: Sham comparator<br>* Sham comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4 | Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24 | Participants score the severity of their symptoms and social/emotional consequences of CS on a 6-point scale: 0 = no problem, 1 = very mild problem, 2 = mild or slight problem, 3 = moderate problem, 4 = severe problem, 5 = problem as bad as it can be. The scores are summed in the range of 0-110; higher scores indicate higher severity of symptoms or social/emotional consequences of CS. | 24 weeks | 
| CFBL in Chronic Sinusitis Symptom Scores at Week 24 | Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS. | Week 24 | 
| Participants With Improved Bilateral Zinreich Score at Week 24 | Each sinus is assigned a score based on the percentage of opacification as follows: 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76 % to 99%, 5 = 100% or completely occluded. Each sinus pair has a bilateral score in the range of 0 to 10. Higher scores indicate higher severity of sinus opacification. Responder is defined as a participant with at least a 1-point decrease in the imaging score at Week 24 compared with baseline. | Week 24 | 
| The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks | To evaluate the safety and tolerability of LYR-210 | 24 weeks | 
| Plasma Drug Concentrations of MF at Week 4 | To evaluate the pharmacokinetics of LYR-210 | 4 Weeks | 
| Plasma Drug Concentrations of MF at Week 12 | To evaluate the pharmacokinetics of LYR-210 | 12 weeks |