Efficacy and Safety of 186 mcg of OPN-375 Nasal Spray Twice a Day (BID) in Adolescents With Chronic Rhinosinusitis Without Nasal Polyps

Inclusion Criteria: 1. Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening) 2. Female subjects, if sexually active, must: 1. be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method \[e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel\], 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 abstinent. 3. Females 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. Must have endoscopic evidence of nasal mucosal disease, with edema, or purulent discharge bilaterally, or presence of bilateral disease on a prior computed tomography (CT) scan performed within 14 days of Visit 1. 6. 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. 7. 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. 8. Must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization. 9. Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2021 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening), and are expected to remain on it throughout the study. Subjects receiving inhaled fluticasone alone or in combination may not participate in the PK sub-study. 10. 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. 11. Must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma) at the screening visit 12. If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to Visit 1 (Screening), and agree to not change the dose of these medications until after Week 4 of the study. 13. 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). 14. Must be capable, in the opinion of the investigator, of providing assent and parent or guardian must provide 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 that they are willing to participate in the study. Exclusion Criteria: 1. Females 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. History of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery. 7. 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). 8. Have a paranasal sinus or nasal tumor. 9. Have a nasal polyp score of grade 1 or greater in either nostril as determined by the nasoendoscopy at screening. 10. Have a nasal septum perforation. 11. Have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening). 12. Have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy. 13. Have current, ongoing rhinitis medicamentosa (rebound rhinitis). 14. Have significant oral structural abnormalities (eg, a cleft palate). 15. Have a diagnosis of cystic fibrosis. 16. History of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). 17. 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. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution. 18. Planned sinonasal surgery during the period of the study. 19. Allergy, hypersensitivity, or contraindication to corticosteroids or steroids. 20. Has used oral steroids in the past for treatment of CS and did not experience any relief of symptoms. 21. Has a steroid eluting sinus stent still in place within 30 days of Visit 1. 22. Allergy or hypersensitivity to any excipients in study drug. 23. Exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD. 24. Have nasal or oral candidiasis. 25. History or current diagnosis of any form of glaucoma or ocular hypertension. 26. History of IOP elevation on any form of steroid therapy. 27. History or current diagnosis of the presence (in either eye) of a cataract unless both natural intraocular lenses have been removed. 28. History of immunodeficiency of any etiology (including poor nutrition) that would be anticipated to affect the likelihood of benefit or harm from the therapeutic intervention. 29. 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. 30. Have a positive drug screen or a 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. 31. Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening). 32. Have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), benralizumab (Fasenra™), Tezepelumab-ekko (Tezspire®) or any other immune-modifying monoclonal antibody within 6 months of Visit 1 (Screening). 33. Is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole, cobicistat). 34. Has a parent, guardian or caregiver who 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. 35. Patients who report unexplained worsening of vision within the past 3 months.