Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

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All Conditions

Neoplasms

Digestive System Diseases

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Nasal Polyps

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Nasopharyngeal Neoplasms

Polyps

Intestinal Neoplasms

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Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

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Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Nose Diseases

Respiratory Tract Diseases

Pathological Conditions, Anatomical

Anti-Allergic Agents

Anti-Inflammatory Agents

Dermatologic Agents

Respiratory System Agents

All Drugs and Chemicals

Fluticasone

Xhance

Bronchodilator Agents

Anti-Asthmatic Agents

Double-Blind Treatment Phase: OPN-375 100 μg BID x 16 weeks

Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks

Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks

Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks

Double-Blind Treatment Phase: OPN-375 200 μg BID x 16 weeks

Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks

Double-Blind Treatment Phase: OPN-375 400 μg BID x 16 weeks

Open-Label Extension Phase: OPN-375 400 μg BID x 8 weeks

Delivered via Optinose Exhalation Delivery System

Fluticasone Propionate

The primary objective of this study is to compare the efficacy of intranasal administration of 100, 200, and 400 μg of fluticasone propionate twice a day delivered by the OptiNose device with placebo in subjects with bilateral nasal polyposis. Two co-primary endpoints will be used in the study: reduction of nasal congestion/obstruction symptoms at the end of Week 4 of the double-blind treatment phase measured by the 7 day average instantaneous AM diary symptom scores, and reduction in total polyp grade (sum of scores from both nasal cavities) over the 16 weeks of the double-blind treatment phase as determined by the Lildholdt scale score measured by nasoendoscopy.

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to assess the efficacy and safety of intranasal administration of 3 doses of OPN-375 (100, 200, and 400 µg bid) in subjects with bilateral nasal polyposis and nasal congestion.

This study consisted of 3 phases. After signing informed consent, subjects who met eligibility criteria at Visit 1 (screening) entered the study.

1. Pretreatment phase (single-blind, placebo, run-in): 7 to up to 14 days duration, to determine disease status eligibility and to ensure the subject was able to comply with study procedures prior to randomization and enrolment in the double-blind treatment phase.
2. Double-blind treatment phase: 16 weeks duration with 6 scheduled visits starting with Visit 2, Day 1 (baseline) when eligible subjects were randomized by balance allocation to 1 of 4 treatment groups and ending at Visit 7 (Week 16).
3. Open-label extension phase: 8 weeks duration with 1 scheduled visit (Visit 8 \[Week 24\]).

Study Evaluating the Efficacy and Safety of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Twice a Day (BID) Using a Novel Bi Directional Device in Subjects With Bilateral Nasal Polyposis Followed by an 8-Week Open-Label Extension Phase to Assess Safety

A 16-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Twice a Day (BID) Using a Novel Bi Directional Device in Subjects With Bilateral Nasal Polyposis Followed by an 8-Week Open-Label Extension Phase to Assess Safety

Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.

0: None

1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated
2. Moderate, definite awareness of symptoms that is bothersome but tolerable
3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living

The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 4 Visit of the double-blind treatment phase

Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. A summary of the changes from baseline to Week 16 in total polyp grade.

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

Reduction in total polyp grade (sum of scores from both nasal cavities) at Week 16 of double-blind treatment phase; Included patients with nasal polyps at baseline

Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.

0: None

1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated
2. Moderate, definite awareness of symptoms that is bothersome but tolerable
3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living

The change from baseline in instantaneous morning diary symptom scores averaged over 7 days prior to the Week 16 Visit of the double-blind treatment phase

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 it can be

The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity.

The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function.

The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.

The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.

Subject responses to the question: "Since starting the study drug, how would you rate the change in your symptoms?" Percentage includes patients who scored either "very much improved," "much improved," or "minimally improved."

The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point.

Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril.

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

A subject was considered eligible for surgical intervention if the following conditions were met:

* Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months.
* Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks.
* Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks.
* Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril).

Optinose US Inc.

The Safety Analysis Set (SAS) included all ITT subjects who received at least 1 dose of study drug. The SAS was used for the analysis of safety. The treatment group classification in the SAS was according to the treatment actually received.

100 μg BID or 200 μg BID or 400 μg Matching Placebo BID x 16 weeks

Placebo (Double-Blind Phase)

OPN-375 100 μg BID (Double-Blind Phase)

OPN-375 200 μg BID (Double-Blind Phase)

OPN-375 400 μg BID (Double-Blind Phase)

OPN-375 400 μg (Open-Label Phase)

Matching Placebo BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

Placebo

OPN-375 100 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 100 μg BID

OPN-375 200 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 200 μg BID

OPN-375 400 μg BID x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 400 μg BID

Total

Age, Continuous

Sex: Female, Male

White

Black/African American

Asian

Other

Race/Ethnicity, Customized

Canada

Czechia

United Kingdom

Ukraine

United States

South Africa

Region of Enrollment

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

These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Included patients with nasal polyps at baseline

Total Polyp Grading Score (sum of scores from both nasal cavities)

Use of intranasal corticosteroid (ICS) treatment for polyps in past 10 years

Patients may have had both sinus surgery and polypectomy.

Previous sinus surgery for polyp removal or sinus surgery

Previous polyp removal surgery via polypectomy only

Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.

0: None

1. Mild - symptoms clearly present, but minimal awareness, and easily tolerated
2. Moderate - definite awareness of symptoms that is bothersome but tolerable
3. Severe - symptoms that are hard to tolerate, cause interference with activities or daily living

These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Nasal Congestion/Obstruction Score (7-Day Instantaneous Morning)

Rhinorrhea Score (7-day instantaneous morning)

Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing.

0: None

1. Mild - Symptoms clearly present, but minimal awareness, and easily tolerated
2. Moderate - Definite awareness of symptoms that is bothersome but tolerable
3. Severe - Symptoms that are hard to tolerate, cause interference with activities or daily living

Facial Pain or Pressure Score (7-day instantaneous morning)

These data are reported for the Full Analysis Set, which included all subjects who received at least one dose of study drug, an who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Hyposomia Score (7-day instantaneous morning)

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

Sinonasal Outcome Test 22 (SNOT-22) Total Score

Medical Outcomes Study Sleep Scale Revised (MOS Sleep-R)

Rhinosinusitis Disability Index (RSDI) Total Score

Short Form (36) Health Survey Version 2 (SF-36v2) - Mental Component

Short Form (36) Health Survey Version 2 (SF-36v2) - Physical Component

Peak Nasal Inspiratory Flow (PNIF)

Nasal Polyp Surgery Eligibility

Vice President Global Clinical Operations & Outsourcing

Matching Placebo Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

Missing data were imputed using the multiple imputation method in the primary analyses for the co-primary efficacy variables. For other efficacy analyses, missing or invalid values were not imputed.

Change in 7-day Average Instantaneous Morning Diary Congestion/Obstruction Symptoms

Change in Total Polyp Grade

100 μg Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 100 μg Twice Daily

200 μg Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 200 μg Twice Daily

OPN-375 400 μg Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

OPN-375 400 μg Twice Daily

Congestion/Obstruction Scores (7-day Instantaneous Morning)

Change in Rhinorrhea Score (7-day Instantaneous Morning)

Facial Pain or Pressure Score (7-day Instantaneous Morning)

Hyposmia Score (7-day Instantaneous Morning)

Change from baseline to Week 16

Change from baseline to Week 24 (all pts on 400 μg

Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

MOS Sleep-R Score

Week 16

Week 24 (all pts on 400 μg OPN-375 BID wks 17-24)

SF-36v2 - Mental Component

SF-36v2 - Physical Component

Patient Global Impression of Change (PGIC) Score

400 μg Twice Daily x 16 weeks, then OPN-375 400 μg (open-label) BID x 8 weeks

Polyp Grade of 0 in at Least One Nostril

Week 24 (all pts on OPN-375 400 mcg BID wks 17-24)

Matching placebo BID x 16 weeks, then OPN-375 (open-label) 400 μg BID x 8 weeks

Spots Global Cancer Trial Database for bilateral nasal polyposis