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
Condition: Chronic Rhinosinusitis
MeSH terms: Sinusitis; Nasal Polyps
Intervention: OPN-375
Intervention description: OPN-375, BID
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 332.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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