Anti-Inflammatory Agent in Sinusitis

Study Overview
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Brief Summary
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To evaluate the efficacy of an anti-inflammatory agent compared with placebo in relieving signs and symptoms of disease in patients with sinusitis.

Detailed Description
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This is a Phase 2a, single-center, randomized, placebo-controlled, double-blind study that includes 12 weeks of treatment with experimental drug anti-inflammatory agent or placebo TID administered orally. All subjects will be ≥18 years, have sinusitis with persistent symptoms despite standard of care treatment, and have failed a course of steroids in the past.

Official Title
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A Phase 2A, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy of an Anti-Inflammatory Agent in Patients With Sinusitis

Conditions
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Nasal Polyps

Intervention / Treatment
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* Drug: AZ compound
* Other: Collection of Biological Specimens
* Drug: Intranasal corticosteroid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Females must have a negative urine pregnancy test at screening unless documented to have a hysterectomy or be postmenopausal. Exclusion Criteria: Inability or unwillingness of a participant to give written informed consent or comply with study protocol Use of any investigational drugs within 30 days of screening. Acute infection needing antibiotic treatment at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: AZ Compound<br>40 mg 12 weeks TID po | Drug: AZ compound<br>* 40 mg three times daily po for 12 weeks<br>Other: Collection of Biological Specimens<br>* collection of biomarkers for analysis of nasal disease<br>* Other names: Biomarkers;Drug: Intranasal corticosteroid<br>* QD Nasal Spray<br>* Other names: Nasal Steroid (Nasonex, Flonase);|
| Placebo Comparator: Placebo<br>40 mg 12 weeks TID po | Other: Collection of Biological Specimens<br>* collection of biomarkers for analysis of nasal disease<br>* Other names: Biomarkers;Drug: Intranasal corticosteroid<br>* QD Nasal Spray<br>* Other names: Nasal Steroid (Nasonex, Flonase);Drug: Placebo<br>* looks like AZ compound, made by same company, double blind. 40 mg three times daily po for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TOTAL POLYP SCORE (TPS) | Measure Description: Measurement of Primary outcome- 0-4 scale in each nostril, total is 8. The total polyp score is the sum of the right and left nasal polyp score. Maximum is 8, minimum is 0. Higher score indicates worse disease. 0 =No polyps 1=Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate 2=Polyps reaching the lower border of the middle turbinate or polyp medial to the middle turbinate 3 = Large polyps reaching the lower border of the inferior turbinate 4 =Large polyps causing complete obstruction. The primary outcome measured change in polyp size and secondary outcomes included change in radiographic severity of sinus disease, quality of life, and nasal symptoms as measured by Sino Nasal Outcome Test-22 (SNOT-22) and sense of smell by Brief Smell Identification Test (B-SIT) at 12 weeks in the AZD1981 group vs. the placebo. These were done at the baseline visit and the Week 12 visit. | Baseline and Week 12 | 
| Sinus CT Scan Scores by Lund-Mackay Scores | Measurement of secondary outcome: sinus CT scan scores by Lund-Mckay scores. We measured sinus radiographic severity with Lund-Mackay scores of 0 to 24. 0 was the least severe and 24 was the most severe. This secondary outcomes included change in radiographic severity of sinus disease, as measured by sinus CT scan scores at baseline and 12 weeks in the AZD1981 group vs. the placebo group. | Baseline and Week 12 | 
| BSIT (Brief Smell Identification Test) | Measurement of secondary outcome- BSIT (brief smell identification test) is a 12-item test measuring sense of smell. This is a multiple choice test with one correct answer out of four possible answer choices. This test features distinct types of smells. Minimum score: 0/12, which indicates that none of the correct answers were chosen on the 12-item test. Maximum score: 12/12, which indicates that all of the correct answers were chosen on the 12-item test. The higher the score, the better the outcome. Only one out of the four possible answer choices for each multiple choice question is correct. There are no subscales. This secondary outcome measures sense of smell by Brief Smell Identification Test (B-SIT) at baseline (visit 1) and 12 weeks (visit 5) in the AZD1981 group vs. the placebo group. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT-22 (Sino-Nasal Outcome Test-22) Score | Measurement of secondary outcome- the SNOT-22 test contains 22 items regarding patient-reported outcomes of sino-nasal symptom severity on a 0-5 scale for each item. 0 is no problem and 5 is problem as bad as it can be, so higher values represent a worse outcome than lower values. The subscale is 0 - 5 of each of the 22 items and the total score is the sum of the subscales of all 22 items. The minimum total score is 0/110. The maximum total score is 110/110. This secondary outcome measured change in patient-reported outcomes of nasal symptoms as measured by Sino Nasal Outcome Test-22 (SNOT-22) over 12 weeks in the AZD1981 group vs. the placebo group. | Baseline and Week 12 | 
| Visual Analog Scale (VAS) | Measurement of secondary outcome- 0 to 10 scale bilaterally that measures how subjective sinus symptom severity, with 0 being the least troublesome to 10 being the most troublesome over 12 weeks in the AZD1981 group vs. the placebo group. | Baseline and Week 12 |