Efficacy & Safety of OPN-375 Adults With Bilateral Nasal Polyps Using Nasoendoscopic Video

The primary objective of this study is to evaluate the efficacy and safety of OPN-375 186 μg twice a day in adults with Bilateral Nasal Polyps using Nasoendoscopic video. The secondary objectives of this study are to evaluate the safety of OPN-375 via adverse event reports, vital signs, and nasal examination. In addition, to measure any change in subject symptoms and functioning from Baseline to 12 and 24 weeks during the study, using the Sinonasal Outcome Test -22 (SNOT-22), Patient's Global Impression of Change (PGIC), and measurement of nasal polyps by independent, blinded reader, and any changes throughout the study.

• Fluticasone Propionate (Drug): OPN-375 186 μg BID, Delivered via exhalation delivery system

Primary outcomes

• Change From Visit 1 at End of Study in Bilateral Nasal Polyp Grade Using Endoscopic Video [Week 24]: : Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate

Secondary outcomes

• Assessment for Safety by Recording Adverse Events and Adverse Events of Special Interests [24 Weeks, up to 30 days after last dose]
• Assessment for Safety Through Nasal Examination [24 Weeks, up to 30 days after last dose]: Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum. If present, the nostril location is also recorded, along with severity, and if there is any relation to an injury or trauma
• Assessment for Safety From Recording Vital Sign - Blood Pressure [Baseline, Week 12, Week 24]: Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
• Assessment for Safety From Recording Vital Sign - Pulse [Baseline, Week 12, Week 24]: measure pulse in beats per minute (bpm)
• Assessment for Safety From the Collection of Information for Concomitant Medications Usage [24 Weeks, up to 30 days after last dose]
• Total Polyp Grading Score (Sum of Scores From Both Nasal Cavities) [Week 24]: Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
• Number of Subjects With a Change of Greater Than or Equal to 1 Point in Bilateral Polyp Grade [Week 24]: Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
• Number of Subjects With a Polyp Grade of 0 on at Least One Side of the Nose at Each Visit [Week 24]: Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate
• Sinonasal Outcome Test 22 (SNOT-22) Total Score [Week 24]: SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst. 0: No problem 1. Very mild problem 2. Mild or slight problem 3. Moderate problem 4. Severe problem 5. Problem as bad as can be
• Sniffin' Sticks N-butanol Test [Week 24]: The Sniffin' Sticks n-butanol (Extended test) are used to investigate human olfactory performance by use of odor pens. the Extended Test consists of 3 different subtests: Threshold, Discrimination and Identification. the Threshold test is used to ascertain the patient's olfactory threshold. the Discrimination test requires the patient to differentiate smells. The Identification test requires the patient to identify everyday smells by means of a card with different choices. The result of this test is expressed as the sum of the results of the 3 subtests, the so called TDI score (threshold, discrimination, identification). A score of more than 30 rates as normal, a score of 30 or less indicates hyposmia and a score of 15 and below point to functional anosmia in form of complete loss of the sense of smell or an extremely weakened smell ability.
• Number of Participants With a PGIC Score of Minimally/Much/Very Much Improved [Week 24]: The Patient Global Impression of Change (PGIC), is a questionnaire where the patient rates the change in their symptoms. Score range is from 1 (very much improved) to 7 (very much worse)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Men or women aged 18 years and older at Visit 1 (Baseline/Day1)
2. Women of child bearing potential must be abstinent, or if sexually active,

   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 postmenopausal (amenorrhea for at least 1 year).
3. Women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Day 1/Baseline)
4. Must have bilateral nasal polyposis with a grade of 2 or 3 in at least one side of the nasal cavity as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Day 1/Baseline)
5. Must have a SNOT-22 score of ≥20 at Visit 1(Baseline/Day 1)
6. Must have been on an adequate dose of an intranasal corticosteroid (e.g. fluticasone propionate, fluticasone furoate, mometasone, triamcinolone, ciclosenide, budesonide, budesonide respules, beclomethasone) for at least 1 month, in the previous 3 months prior to Visit 1 (Day 1/Baseline)
7. Subjects with comorbid asthma or chronic obstructive pulmonary disease (COPD) must be stable with no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before the screening visit. 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 screening with plans to continue use throughout the study
8. Must be able to cease treatment with oral steroids, intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at Visit 1 (Day 1/Baseline)
9. Must demonstrate correct use of the demo EDS
10. Ability to read and speak English
11. 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

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. Have used XHANCE™ (fluticasone propionate) nasal spray within the past 2 months
4. Nasal septum perforation
5. Has had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Day 1/Baseline)
6. Have evidence of significant mucosal injury or ulceration (e.g. exposed cartilage) on Visit 1 (Day 1/Baseline) nasal examination/nasoendoscopy
7. History of sinus or nasal surgery within 3 months before Visit 1 (Day 1/Baseline). If >3 months subject should be fully recovered from surgery
8. Current, ongoing rhinitis medicamentosa (rebound rhinitis)
9. Have significant oral structural abnormalities, e.g., a cleft palate
10. Diagnosis of cystic fibrosis
11. History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
12. Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Day 1/Baseline). Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution
13. Planned sinonasal surgery during the period of the study
14. Allergy, hypersensitivity, or contraindication to corticosteroids, steroids, or to any excipients in OPN-375
15. Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral, parenteral, intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Day 1/Baseline); except as noted in inclusion criteria for subjects with comorbid asthma or COPD
16. Have nasal candidiasis at Visit 1 (Day 1/Baseline)
17. History or current diagnosis of any form of glaucoma, ocular hypertension, or intraocular pressure elevation on any form of steroid therapy
18. History or current diagnosis of the presence (in either eye) of a sub-capsular cataract
19. 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
20. Recent (within 1 year of Visit 1 (Day 1/Baseline)) 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
21. Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Day 1/Baseline)
22. Employees 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, as well as family members of the employees or the investigator

Participant flow

Outcome results

• Change From Visit 1 at End of Study in Bilateral Nasal Polyp Grade Using Endoscopic Video (Primary), Mean, units on a scale: OPN-375 186 mcg BID -0.7 +/- 0.9
• Assessment for Safety by Recording Adverse Events and Adverse Events of Special Interests (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 1
• Assessment for Safety Through Nasal Examination (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 1
• Assessment for Safety From Recording Vital Sign - Blood Pressure (Secondary), Mean, mmHg: OPN-375 186 mcg BID - Systolic BP 130.1 +/- 14.3; OPN-375 186 mcg BID - Diastolic BP 83.3 +/- 9.3
• Assessment for Safety From Recording Vital Sign - Pulse (Secondary), Mean, bpm: OPN-375 186 mcg BID 71.5 +/- 7.1
• Assessment for Safety From the Collection of Information for Concomitant Medications Usage (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 1
• Total Polyp Grading Score (Sum of Scores From Both Nasal Cavities) (Secondary), Mean, units on a scale: OPN-375 186 mcg BID 2.4 (2 to 4)
• Number of Subjects With a Change of Greater Than or Equal to 1 Point in Bilateral Polyp Grade (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 5
• Number of Subjects With a Polyp Grade of 0 on at Least One Side of the Nose at Each Visit (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 1
• Sinonasal Outcome Test 22 (SNOT-22) Total Score (Secondary), Mean, units on a scale: OPN-375 186 mcg BID 27.8 +/- 16.1
• Sniffin' Sticks N-butanol Test (Secondary), Mean, units on a scale: OPN-375 186 mcg BID 16.5 +/- 6.9
• Number of Participants With a PGIC Score of Minimally/Much/Very Much Improved (Secondary), Count of participants, Participants: OPN-375 186 mcg BID 9

Adverse events

Time frame: 24 weeks, and up to 30 days after the last dose

Other adverse events by term

• Informed Consent Form (PDF, 2018-02-20)
• Study Protocol and Statistical Analysis Plan (PDF, 2018-01-30)

• Jennifer Carothers, Study director, Optinose US Inc.
• John Messina, Study chair, Optinose US Inc.