A Study to Evaluate 611 in Patients With Chronic Rhinosinusitis With Nasal Polyps

Study Overview
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Brief Summary
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This study will evaluate the effect and safety of 611 in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).

Detailed Description
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The main purpose is to evaluate the effect of 611 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in eligible patients with CRSwNP whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison to placebo.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase II Clinical Study to Evaluate the Efficacy and Safety of 611 in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Conditions
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Sinusitis, Nasal Polyps, Polyps

Intervention / Treatment
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* Drug: 611
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male patients aged ≥18 and ≤ 75 years at the time of screening. Bilateral CRSwNP. Bilateral NPS of ≥5 with a minimum score of 2 in each nasal cavity Nasal Congestion Score of > 2 at screening and a weekly average severity of > 1 at time of randomization. Patients whose bilateral sino-nasal polyposis remains inadequately controlled despite prior treatment with SCS anytime within the past 2 years; and/or had a medical contraindication/intolerance to SCS; and/or received nasal polyp surgery 6 months before signing the ICF. Exclusion Criteria: Patients with other nasal diseases or symptoms. Patients who are taking or have taken the following prohibited therapies as specified, e.g., systemic steroids within 4 weeks prior to screening, less than 3 months or 5 half-lives for biologic therapy prior to screening. Patients who have active Hepatitis B, Hepatitis C or HIV infections as determined by positive results at Screening. History of cancer. Known or suspected history of immunosuppression. Known with allergic or intolerant to mometasone furoate spray or 611/placebo.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 611 Dose A<br>611 300 mg Q2W, subcutaneous (SC) injection. | Drug: 611<br>* 611 subcutaneous (SC) injection.<br>|
| Experimental: 611 Dose B<br>611 450 mg Q4W, subcutaneous (SC) injection. | Drug: 611<br>* 611 subcutaneous (SC) injection.<br>|
| Placebo Comparator: Placebo<br>Placebo subcutaneous (SC) injection. | Drug: Placebo<br>* Placebo subcutaneous (SC) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 16 in Bilateral Nasal Polyp Score (NPS) | NPS is evaluated by nasal endoscopy. For each nostril, NPS is graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity; lower score = smaller sized polyps. Bilateral NPS is the sum of right and left nostril scores, ranges from 0 (no polyps) to 8 (large polyps), higher score = more severe disease. | Up to 16 weeks | 
| Change From Baseline at Week 16 in Nasal Congestion Symptom Severity Score (NCS) | NCS is assessed by the participants daily from visit 1 and throughout the study on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicates more severity. | Up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of study in Lund Mackay Score | The Lund Mackay Score scoring system rates each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score is the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. | Up to 16 weeks | 
| Change From Baseline to the End of study in Total Nasal Symptom Score (TNSS) | TNSS is a composite of nasal congestion, loss of smell, and rhinorrhea (anterior/posterior nasal discharge), each access on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranges from 0 (no symptoms) to 12 (severe symptoms). Higher score indicated more severe symptoms. | Up to 16 weeks | 
| Change From Baseline to the End of study in the University of Pennsylvania Smell Identification Test (UPSIT) Score | The UPSIT is a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia) to 40 (normal sense of smell), lower score indicated severe smell loss. | Up to 16 weeks | 
| Change From Baseline to the End of study in 22-item Sino-nasal Outcome Test (SNOT-22) Scores | The SNOT-22 is a validated questionnaire that used to assess the impact of chronic rhinosinusitis phenotype with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). It is a 22 item questionnaire with each item assigned a score ranging from 0 (no problem) to 5 (problem as bad as it can be). The total score may range from 0 (no disease) to 110 (worst disease), lower scores representing better health related quality of life. | Up to 16 weeks | 
| 611 Concentration in Serum | The concentration of 611 in Serum. | Up to 24 weeks |