LYR-220 for Adult Subjects With Chronic Rhinosinusitis (BEACON Study)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, pharmacokinetics and efficacy of two LYR-220 designs in symptomatic adult chronic rhinosinusitis (CRS) subjects who have had a prior functional endoscopic sinus surgery.

Detailed Description
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This is a Phase II, Patient-blinded, Two-part, Randomized, Parallel-group Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of LYR-220. The study will consist of two parts: Part 1 will enroll up to 10 patients and is open label. Part 2 is randomized, sham controlled and will enroll approximately 40 patients. The study follow-up duration is 28 weeks.

Official Title
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BEACON: A Phase II, Patient-blinded, Two-part, Randomized, Parallel-group Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of LYR-220 in Chronic Rhinosinusitis (CRS) Patients Who Have Had a Prior Ethmoidectomy

Conditions
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Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)

Intervention / Treatment
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* Drug: LYR-220 Design 1
* Drug: LYR-220 Design 2
* Drug: Bilateral sham procedure control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic rhinosinusitis. Has had a prior bilateral total ethmoidectomy. Has computed tomography (CT) ethmoid cavity opacification. Has a Sinonasal Outcome Test (SNOT-22) ≥ 20 at Screening Visit. Minimum cardinal symptom score. 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 or regulatory authority if applicable by national law. Agrees to comply with all study requirements. Exclusion Criteria: 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. Had dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. Past or present functional vision in only one eye. Past, present, or planned organ transplant or chemotherapy with immunosuppression. With prior cataract surgery or presence (in either eye) of posterior subcapsular cataract of grade 2 or higher, nuclear cataract of grade 3 or higher, or cortical cataract of grade 2 or higher or involving a minimum of center optic zone of 3 mm diameter. Ethmoidectomy that was unilateral or partial. 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: Treatment Arm A: LYR-220 Design 1<br>Bilateral insertion of LYR-220 drug matrix (mometasone furoate 7500 µg) Design 1 | Drug: LYR-220 Design 1<br>* LYR-220 drug matrix (mometasone furoate 7500 µg) Design 1<br>|
| Experimental: Treatment Arm B: LYR-220 Design 2<br>Bilateral insertion of LYR-220 drug matrix (mometasone furoate 7500 µg) Design 2 | Drug: LYR-220 Design 2<br>* LYR-220 drug matrix (mometasone furoate 7500 µg) Design 2<br>|
| Sham Comparator: Treatment Arm C: Bilateral sham procedure control<br>Bilateral sham procedure control | Drug: Bilateral sham procedure control<br>* Bilateral sham procedure control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Product-related unexpected serious adverse events | Product-related unexpected serious adverse events | Through Week 28 | 
| Plasma MF concentrations | Plasma MF concentrations | Through Week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Severity and percentage of subjects reporting treatment-emergent adverse events and serious adverse events | Through Week 28 | 
| Laboratory Values (hematology and chemistry) | Percentage of subjects with abnormal and clinically significant abnormal laboratory values | Through Week 25 | 
| Endoscopic findings | Percentage of subjects with newly identified or worsened endoscopic findings in the ethmoid cavity (mild, moderate, or severe) | Through Week 25 | 
| Ophthalmic Assessment: Intraocular Pressure (IOP) | Percentage of subjects with clinically significant increase in IOP | Through Week 25 | 
| Ophthalmic Assessment: Cataract | Percentage of subjects with newly identified or worsened cataract in one or both eyes | Through Week 25 | 
| Improving Chronic Rhinosinusitis (CRS) specific Quality of Life as per the 22-item sino-nasal outcome test (SNOT-22) questionnaire | Change from baseline in total patient-reported outcome measures. Each symptom is scored as it has been over the past two weeks on a 6-point scale (0 to 5: 0 = no problem to 5 = problem as bad as it can be). Higher scores indicate severity of symptoms. | Through Week 28 | 
| Change in Chronic Rhinosinusitis (CRS) symptom scores | Change from baseline in the average composite score | Through Week 28 |