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

Study Overview
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Brief Summary
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This is a 24-week, open-label, multi-center study designed to assess the efficacy and safety of OPN-375 186 μg twice a day in subjects with nasal polyps using Nasoendoscopic video. The total planned number of subjects is approximately 10, with each subject receiving OPN-375 186 μg twice a day.

Detailed Description
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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.

Official Title
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A 24-Week Open-Label Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day (BID) in Adults With Bilateral Nasal Polyps Using Nasoendoscopic Video

Conditions
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Nasal Polyposis

Intervention / Treatment
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* Drug: Fluticasone Propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 years and older at Visit 1 (Baseline/Day1) Women of child bearing potential must be abstinent, or if sexually active, 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 be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or be postmenopausal (amenorrhea for at least 1 year). Women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Day 1/Baseline) 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) Must have a SNOT-22 score of ≥20 at Visit 1(Baseline/Day 1) 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) 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 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) Must demonstrate correct use of the demo EDS Ability to read and speak English 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: Women who are pregnant or lactating Inability to have each nasal cavity examined for any reason, including nasal septum deviation Have used XHANCE™ (fluticasone propionate) nasal spray within the past 2 months Nasal septum perforation Has had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Day 1/Baseline) Have evidence of significant mucosal injury or ulceration (e.g. exposed cartilage) on Visit 1 (Day 1/Baseline) nasal examination/nasoendoscopy 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 Current, ongoing rhinitis medicamentosa (rebound rhinitis) Have significant oral structural abnormalities, e.g., a cleft palate Diagnosis of cystic fibrosis History of Churg-Strauss syndrome or dyskinetic ciliary syndromes 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 Planned sinonasal surgery during the period of the study Allergy, hypersensitivity, or contraindication to corticosteroids, steroids, or to any excipients in OPN-375 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 Have nasal candidiasis at Visit 1 (Day 1/Baseline) History or current diagnosis of any form of glaucoma, ocular hypertension, or intraocular pressure elevation on any form of steroid therapy History or current diagnosis of the presence (in either eye) of a sub-capsular cataract 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 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 Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Day 1/Baseline) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPN-375 186 mcg BID<br> | Drug: Fluticasone Propionate<br>* OPN-375 186 μg BID, Delivered via exhalation delivery system<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 24 Weeks, up to 30 days after last dose | 
| Assessment for Safety From Recording Vital Sign - Blood Pressure | Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg) | Baseline, Week 12, Week 24 | 
| Assessment for Safety From Recording Vital Sign - Pulse | measure pulse in beats per minute (bpm) | Baseline, Week 12, Week 24 | 
| 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) | Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps Mild polyposis: polyps not reaching below the inferior border of the middle turbinate Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate | Week 24 | 
| Number of Subjects With a Change of Greater Than or Equal to 1 Point in Bilateral Polyp Grade | Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps Mild polyposis: polyps not reaching below the inferior border of the middle turbinate Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate | Week 24 | 
| Number of Subjects With a Polyp Grade of 0 on at Least One Side of the Nose at Each Visit | Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps Mild polyposis: polyps not reaching below the inferior border of the middle turbinate Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate | Week 24 | 
| Sinonasal Outcome Test 22 (SNOT-22) Total Score | 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 Very mild problem Mild or slight problem Moderate problem Severe problem Problem as bad as can be | Week 24 | 
| Sniffin' Sticks N-butanol Test | 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. | Week 24 | 
| Number of Participants With a PGIC Score of Minimally/Much/Very Much Improved | 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) | Week 24 |