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

Purpose

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.

Condition

  • Chronic Rhinosinusitis

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
OPN-375 186 μg BID
OPN-375 186 μg BID x 24 Weeks
  • Drug: OPN-375
    OPN-375, BID
Active Comparator
OPN-375 372 μg BID
OPN-375 372 μg BID x 24 Weeks
  • Drug: OPN-375
    OPN-375, BID
Placebo Comparator
Placebo
Matching Placebo BID x 24 Weeks
  • Drug: OPN-375
    OPN-375, BID

More Details

Status
Completed
Sponsor
Optinose US Inc.

Study Contact

Detailed 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.