Chronic rhinosinusitis MedDRA version: 20.1 Level: PT Classification code 10009137 Term: Chronic sinusitis System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
OptiNose US, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. men or women aged 18 years and older at baseline visit 2. women of child bearing potential must be abstinent, or if sexually active, a. 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 b. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or c. 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 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 or purulent discharge; or polyps/polypoid tissue <Grade 1 in middle meatus, bilaterally , or presence of bilateral disease on a prior CT scan performed within 14 days of Visit 1 6. must have confirmatory evidence via a computed tomography(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 correctly; all subjects will be required to demonstrate correct use with the practice exhalation delivery system (EDS) at Visit 1 (Screening). 16. must be capable, in the opinion of the investigator, of providing informed consent to participate in the
Exclusion criteria
Exclusion criteria: 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 polyp grade =1 (polyp that is free on 5 sides and has a stalk) on either side of the nose 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, intraarticular, 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 (intraocular pressure [IOP] at screening of >21 mm Hg) 27. history of IOP elevation on any form of steroid therapy 28. history or current diagnosis of the presence (in either eye) of a subcapsular 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The key secondary objectives of this study are to compare the efficacy twice-daily doses of 186 and 372 µg of OPN-375 with placebo on: • change from baseline to Week 24/ET in subject symptoms and functioning, as measured by Sinonasal Outcome Test - 22 (SNOT-22) total score • change from baseline to Week 24/ET in subject symptoms and functioning, as measured by Sinonasal Outcome Test-22 (SNOT-22) total score in subjects who report using an intranasal, topically acting nasal steroid for the treatment of CRS within 30 days of Visit 1 • change in sleep quality from baseline to Week 24/ET, using the Global Pittsburgh Sleep Quality Index (PSQI) Score • frequency of acute exacerbations of CRS over the 24-week treatment period, defined as a worsening of symptoms that requires escalation of treatment ;Primary end point(s): Co-Primary Endpoints: - change from baseline to the end of Week 4 in average total instantaneous morning (AM) scores (evaluation of symptom severity immediately preceding the time of scoring) of: • nasal congestion • nasal discharge (anterior and/or posterior) • facial pain/pressure sensation The baseline CSNS is the average of the total instantaneous AM scores over the last 7 days of the single-blind run-in period, and at the end of Week 4, scores are averaged over 7 days before Week 4. - change from baseline to Week 24 in the APOV in the ethmoid and maxillary sinuses;Timepoint(s) of evaluation of this end point: Please refer to schedule of study procedures and evaluations;Main Objective: 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 (CRS) using the following co-primary endpoints: • change from baseline in symptoms as measured by a composite score of nasal symptoms (CSNS): congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or poster | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: • change from baseline to Week 24/ET in subject symptoms and functioning as measured by SNOT-22 total score • change from baseline to Week 24/ET in SNOT-22 total score in subjects from studies OPN-FLU-CS-3206 and OPN-FLU-CS-3205 (pooled data) who report using an intranasal, topically acting nasal steroid for the treatment of CRS within 30 days of Visit 1 • change from baseline to Week 24/ET in Global PSQI Score from studies OPN-FLU-CS-3206 and OPN-FLU-CS-3205 (pooled data) • frequency of acute exacerbations of CRS over the 24-week treatment period, defined as a worsening of symptoms that requires escalation of treatment from studies OPN-FLU-CS-3206 and OPN-FLU-CS-3205(pooled data) Safety Endpoints: • monitoring adverse events (AEs) throughout the study; results of nasal examinations, vital signs measurements (ie, blood pressure, pulse), and weight; and monitoring concomitant medication usage;Timepoint(s) of evaluation of this end point: Please refer to schedule of study procedures and evaluations | — |
Countries
Australia, Bulgaria, Canada, Czechia, Czech Republic, Georgia, New Zealand, Poland, Romania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Operations
OptiNose US, Inc.
Outcome results
None listed