Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis With or Without the Presence of Nasal Polyps

Chronic Rhinosinusitis Clinical Trial

Official title:

A 24-Week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Rhinosinusitis With or Without the Presence of Nasal Polyps

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03781804
• Other study ID #: OPN-FLU-CS-3205
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2018
• Est. completion date: January 19, 2022

Study information

• Verified date: May 2024
• Source: Optinose US Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic rhinosinusitis (CS) with or without nasal polyps.

Description:

The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints:

1. A change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.

2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 332
• Est. completion date: January 19, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Potential subjects must meet the following criteria to enter this study:

1. men or women aged 18 years and older at baseline visit

2. women of childbearing potential must be abstinent, or if sexually active,

1. be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner sterilization) before entry and throughout the study, or

2. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or

3. be postmenopausal (amenorrhea for at least 1 year)

3. women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)

4. must have a history of chronic rhinosinusitis (CRS) and be currently experiencing 2 or more of the following symptoms, 1 of which has to be either nasal congestion or nasal discharge (anterior and/or posterior nasal discharge) for equal to or greater than 12 weeks:

• nasal congestion

• nasal discharge (anterior and/or posterior nasal discharge)

• facial pain or pressure

• reduction or loss of smell

5. endoscopic evidence of nasal mucosal disease, with edema, purulent discharge, or polyps in middle meatus, bilaterally, or presence of bilateral disease on a prior computed tomography (CT) scan performed within 14 days of Visit 1

6. must have confirmatory evidence via a CT scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of =1)

7. baseline CT scan must show a combined =25% opacification of the ethmoid sinuses and =25% opacification of at least 1 maxillary sinus

8. must have at least moderate symptoms (as defined in protocol) of nasal congestion as reported by the subject, on average, for the 7-day period preceding Visit 1 (Screening) run-in

9. must have an average morning score of at least 1.5 for congestion on the Nasal Symptom Scale (as defined in protocol) recorded on the subject diary over a 7-day period during the first 14 days of the single-blind run-in period

10. must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization

11. Subjects with comorbid asthma or chronic obstructive pulmonary disorder (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 µg/day of beclomethasone (or equivalent) for at least 3 months before Visit 1 (Screening) with plans to continue use throughout the study.

12. Subjects with aspirin-exacerbated respiratory disease, who have undergone aspirin desensitization and are receiving daily aspirin therapy, must be receiving therapy for at least 6 months prior to Visit 1.

13. must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the screening visit

14. must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)

15. must be able to use the exhalation delivery system (EDS) correctly; all subjects will be required to demonstrate correct use with the practice EDS at Visit 1 (Screening).

16. must be capable, in the opinion of the investigator, of providing informed consent to participate in the study. Subjects must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Potential subjects who meet any of the following criteria will be excluded from entering this study:

1. women who are pregnant or lactating

2. inability to have each nasal cavity examined for any reason, including nasal septum deviation

3. inability to achieve bilateral nasal airflow

4. is currently taking XHANCE®

5. have previously used XHANCE for more than 1 month and did not achieve an adequate symptomatic response

6. the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan

7. history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery

8. have current evidence of odontogenic sinusitis, sinus mucocele (the affected sinus is completely opacified and either the margins are expanded and/or thinned OR there are areas of complete bone resorption resulting in bony defect and extension of the "mass" into adjacent tissues), evidence of allergic fungal sinusitis, or evidence of complicated sinus disease (including, but not limited to, extension of inflammation outside of the sinuses and nasal cavity)

9. have a paranasal sinus or nasal tumor

10. have a polyp extending outside the ostiomeatal complex/middle turbinate (anterior or inferior) that is below the inferior turbinate attachment as determined by the nasoendoscopy at screening

11. have a nasal septum perforation

12. have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)

13. have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy

14. have current, ongoing rhinitis medicamentosa (rebound rhinitis)

15. have significant oral structural abnormalities (eg, a cleft palate)

16. have a diagnosis of cystic fibrosis

17. history of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or dyskinetic ciliary syndromes

18. Symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection, influenza, or SARS-CoV-2 (COVID-19) has not occurred before Visit 1 or was less than 4 weeks before the CT scan. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.

19. planned sinonasal surgery during the period of the study

20. allergy, hypersensitivity, or contraindication to corticosteroids or steroids

21. has used oral steroids in the past for treatment of CRS and did not experience any relief of symptoms

22. has a steroid eluting sinus stent still in place within 30 days of Visit 1

23. allergy or hypersensitivity to any excipients in study drug

24. exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD

25. have nasal candidiasis

26. history or current diagnosis of any form of glaucoma or ocular hypertension

27. history of intraocular pressure (IOP) elevation on any form of steroid therapy

28. history or current diagnosis of the presence (in either eye) of a cataract unless both natural intraocular lenses have been removed

29. history of immunodeficiency

30. any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study

31. have a positive drug screen or a recent (within 1 year of Visit 1 [Screening]) history of drug or alcohol abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study

32. have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)

33. have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening)

34. is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole, cobicistat)

35. is an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or is a family member of the employee or the investigator

36. Patients who report unexplained worsening of vision within the past 3 months (e.g. difficulty reading or seeing traffic signs from a distance.). A diagnosis of presbyopia established by an eye doctor is not exclusionary

Related Conditions & MeSH terms

• Chronic Rhinosinusitis
• Nasal Polyps
• Rhinosinusitis
• Sinusitis

Intervention

Drug:
• OPN-375
OPN-375, BID

Locations

Country	Name	City	State
Bulgaria	UMHAT - Kaspela EOOD	Plovdiv
Bulgaria	?inistry of Interior - Medical Institute	Sofia
Bulgaria	MC Iskar	Sofia
Bulgaria	MC Pirogov	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Serdika	Sofia
Bulgaria	The Military Medical Academy (MHAT)	Sofia
Canada	St. Joseph's Healthcare London	London	Ontario
Canada	CHU de Quebec, pavillon Hopital Saint- Sacrement	Québec
Canada	University of British Columbia and Providence Health Care	Vancouver	British Columbia
Georgia	JSC Curatio	Tbilisi
Georgia	Ltd Acad. Fridon Todua Medical Center	Tbilisi
Georgia	Ltd Aversi Clinic	Tbilisi
Georgia	Ltd Israel-Georgian Medical Research Clinic - Helsicore	Tbilisi
Georgia	Ltd Simon Khechinashvili University Hospital	Tbilisi
Poland	ReumaClinic	Bialystok
Poland	Przychodnia "Narutowicza"	Inowroclaw
Poland	Centrum Medyczne Angelius Provita	Katowice	SL
Poland	Jaroslaw Slifirski Indywidualna Praktyka Lekarska	Kety	MA
Poland	Centrum Medyczne All Med - Krakow	Kraków
Poland	Medical Center Wos i Piwowarczyk	Kraków
Poland	Mini Clinic Pawel Bialoglowski	Lancut	PK
Poland	Centrum Alergologii	Lublin
Poland	NZOZ Imedica	Poznan	Wielkopolska
Poland	Centrum Medyczne Lucyna Andrazej Dymek - Strzelce Opolskie	Strzelce Opolskie
Poland	NZOZ "Ignis" dr med. Alicja Lobinska	Swidnik
Poland	NZOZ Przychodnia Medycyny Rodzinnej	Swietochlowice
Poland	NZOZ Centrum Medyczne LiMED	Tarnowskie Góry	SL
Poland	Centrum Medyczne Biotamed	Wieliczka	Malopolskie
Poland	Medicus Sp z o.o.	Wroclaw	Dolnoslaskie
Russian Federation	Central Clinical Hospital with Polyclinic" Office of Affairs of the President of the Russian Federation	Moscow
Russian Federation	I.M. Sechenov First Moscow State Medical University-University Hospital No.1 - Ear, Nose, and Throat Clinic	Moscow	Moskovskaya Obl.
Russian Federation	Moscow Regional Scientific Research Clinical Institute n.a. M.F. Vladimirsky (MONIKI)	Moscow	Moskovskaya Obl.
Russian Federation	Saint-Petersburg Institute of Ear, Nose, Throat, and Speech (The RSFSR Ministry of Health)	Saint Petersburg
Russian Federation	Saint-Petersburg State Medical University n.a. I.P. Pavlov	Saint Petersburg	Saint-Petersburg
Russian Federation	Smolensk, "Uromed"	Smolensk	Smolenskaya Obl
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl	Yaroslavskaya Obl.
Sweden	ONH Kliniken Sahlgrenska Universitetsynkhiset	Gothenburg	Vastra Gotaland Lan
Sweden	Helsingborg Hospital	Helsingborg	Sverige
Sweden	ONH Klinikun Skane Universitetssjukhuset (Lund - Oron- Nas- Och Halskliniken)	Lund	Skane Lan
Sweden	Karolinska University Hospital	Stockholm	Stockholms Lan
Sweden	Sofiahemmet Hospital	Stockholm
United Kingdom	University Hospital of Wales	Cardiff	Cf14 4xw
United Kingdom	Darlington Memorial Hospital	Darlington
United Kingdom	Lister Hospital	Stevenage
United Kingdom	Stockport NHS Foundation Trust (Stepping Hill Hospital Base)	Stockport
United Kingdom	Wrightington, Wigan and Leigh NHS Foundation Trust	Wigan
United States	Emory University MOT	Atlanta	Georgia
United States	Kern Research	Bakersfield	California
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Bellingham Asthma, Allergy & Immunology Clinic	Bellingham	Washington
United States	Specialty Physician Associates	Bethlehem	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Allergy Asthma & Immunology Relief of Charlotte	Charlotte	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The University of Chicago	Chicago	Illinois
United States	Colorado ENT & Allergy	Colorado Springs	Colorado
United States	University of Missouri, Dept of Otorlaryngology	Columbia	Missouri
United States	Iowa Head & Neck	Des Moines	Iowa
United States	Sacramento Ear, Nose & Throat Surgical and Medical Group Inc	Folsom	California
United States	AZ Allergy & Immunology Research	Gilbert	Arizona
United States	University of TX Health Science Ctr at Houston	Houston	Texas
United States	Allergy & Asthma Specialists Medical Group	Huntington Beach	California
United States	Holston Medical Group	Kingsport	Tennessee
United States	Asthma, Allergy, and Immunology Associates, PC	Lincoln	Nebraska
United States	Jonathan Corren, MD, Clinical Research Division	Los Angeles	California
United States	Kentuckiana Ear Nose & Throat	Louisville	Kentucky
United States	Advanced ENT and Allergy	New Albany	Indiana
United States	Yale School of Medicine Section of Otolaryngology	New Haven	Connecticut
United States	ENT and Allergy Associates	New Hyde Park	New York
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Madison ENT and Facial Plastic Surgery	New York	New York
United States	Mount Sinai Downtown Union Square	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Midwest Allergy Sinus Asthma	Normal	Illinois
United States	National Allergy and Asthma Research	North Charleston	South Carolina
United States	Atlantic Research Center	Ocean City	New Jersey
United States	Allergy Asthma & Clinical Research Center	Oklahoma City	Oklahoma
United States	Hospital at the University of PA	Philadelphia	Pennsylvania
United States	Northwest Research Center	Portland	Oregon
United States	Sacramento Ear, Nose & Throat	Roseville	California
United States	UC Davis Medical Center	Sacramento	California
United States	St. Cloud Ear, Nose & Throat	Saint Cloud	Minnesota
United States	Chrysallis Clinical Research	Saint George	Utah
United States	Intermountain Ear, Nose & Throat	Salt Lake City	Utah
United States	STAAMP Research, LLC	San Antonio	Texas
United States	Allergy and Asthma Associates of Santa Clara Valley	San Jose	California
United States	Spokane ENT	Spokane Valley	Washington
United States	Breathe Clear Institute	Torrance	California
United States	Ear, Nose and Throat Associates at Greater Baltimore Medical Center	Towson	Maryland
United States	Vital Prospects Clinical Research Institute, P.C.	Tulsa	Oklahoma
United States	Allergy & Asthma Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Optinose US Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Georgia,  Poland,  Russian Federation,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of Safety by Recording the Severity of Adverse Events (AEs)	Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe	24 Weeks
Other	Evaluation of Safety-Nasal Examination	Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum.	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Blood Pressure	Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Pulse	Measure pulse in beats per minute (bpm)	24 Weeks
Other	Evaluation of Safety Measuring Vital Signs- Weight	Assessment of safety from physical examination-weight measured in kg or lb	24 Weeks
Other	Evaluation of Safety - Monitoring Concomitant Medication Usage	Assessment for safety from the collection of information for concomitant medications usage	24 Weeks
Primary	Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4	Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.	4 Weeks
Primary	Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses	Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.	Baseline, Week 24
Secondary	Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains	The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. Each item is rated as follows: 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.	Week 24
Secondary	Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior)	Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.	Week 12
Secondary	Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores	Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.	12 Weeks
Secondary	Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores	Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. The change reported in the results is calculated by subtracting the score reported at Baseline from the score reported at Visit 4 (Week 12).	12 Weeks
Secondary	Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores	Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.	12 Weeks
Secondary	Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores	Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.; The value reported in the results is calculated by subtracting the score reported by the patient at Baseline from the score reported by the patient at Visit 4 (Week 12).	12 Weeks
Secondary	Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations	Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for CRS with Nasal Polyps (NP) and without NP sub-groups and in patients with and without previous sinus surgery. Percent volume opacified can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefor, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.	24 Weeks
Secondary	Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.	Baseline, Week 24
Secondary	Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).; The values reported for this outcome are the change in total opacification of the left and right maxillary and ethmoid sinuses (Visit 6 [Wk 24] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid).	24 Weeks
Secondary	Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs	Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).; Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at Baseline from the total score at Visit 6 (Wk 24).	Week 24
Secondary	Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment		Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment		Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations	Percent of sinus volume occupied by disease in the worst sinus between maxillary and ethmoid sinuses for the total population, chronic rhinosinusitis with nasal polyps (CRSwNP) subgroup, chronic rhinosinusitis without nasal polyps (CRSsNP) subgroup, patients with previous sinus surgery subgroup, and without previous surgery subgroup.	24 Weeks
Secondary	Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score	Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 50.	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined	Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results are determined by subtracting the total score at Baseline from the total score at Week 24.	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs	Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% Each sinus pair (left and right side) listed below can achieve a total score of 0-10 (sum of score on each side). The values reported for this outcome calculated by subtracting the score at Baseline from the score at Visit 6 (Wk 24).	Baseline, Week 24
Secondary	Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations	Zeinrich Modification of the Lund-Mackay Staging System: Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%	Baseline, Week 24
Secondary	Time Comparison to First Acute Exacerbation of Chronic Sinusitis	Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment	24 Weeks
Secondary	Percentage of Subjects Requiring Rescue Medication After Week 4	Recording of each dose of approved rescue medication after the Week 4 visit through Week 12	8 Weeks
Secondary	Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)	The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 "component" scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome.	12 Weeks, 24 Weeks
Secondary	Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)	Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse	Week 4, Week 24
Secondary	Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)	The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome.	Week 24
Secondary	Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS)	Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.	24 Weeks
Secondary	Change in the SF-36v2 Physical Composite Score (PCS)	Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.	24 Weeks
Secondary	Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)	The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate with a better health status, with 100 representing the highest level of functioning possible.	24 Weeks
Secondary	Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)	The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, with higher scores indicating a worse outcome.	24 Weeks
Secondary	Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™	The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives to identify the odor accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposmia) as well as an index to detect malingering.	24 Weeks
Secondary	Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS)	The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine).	24 Weeks
Secondary	Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument	The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state).	24 Weeks
Secondary	Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery	Percentage of subjects indicating that they are willing to consider Sinus Surgery	Baseline, Week 24
Secondary	Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention	Percentage of Subjects who meet the minimal objective criteria for surgical intervention	Baseline, Week 24
Secondary	Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery	Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. The number of participants analyzed indicates the total number of participants for whom this analysis was completed.	Week 24
Secondary	Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ).	The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. Values for this outcome are reported as the change in relative absenteeism (the percentage of productivity at work) from baseline to Week 24.	24 Weeks