Efficacy & Safety of OPN-375 Adults With Bilateral Nasal Polyps Using Nasoendoscopic Video
Primary Purpose
Nasal Polyposis
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fluticasone Propionate
Sponsored by
About this trial
This is an interventional treatment trial for Nasal Polyposis
Eligibility Criteria
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
Sites / Locations
- University of Colorado SOM, Department of Otolaryngology
- University of Texas Health Science Center at Houston, McGovern Medical School, Dept. of Otolaryngology, Head and Neck Surgery
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
OPN-375 186 mcg BID
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Assessment for Safety by Recording Adverse Events and Adverse Events of Special Interests
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
Assessment for Safety From Recording Vital Sign - Blood Pressure
Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
Assessment for Safety From Recording Vital Sign - Pulse
measure pulse in beats per minute (bpm)
Assessment for Safety From the Collection of Information for Concomitant Medications Usage
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
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
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
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
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.
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03591068
Brief Title
Efficacy & Safety of OPN-375 Adults With Bilateral Nasal Polyps Using Nasoendoscopic Video
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 7, 2018 (Actual)
Primary Completion Date
February 22, 2019 (Actual)
Study Completion Date
February 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Optinose US Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasal Polyposis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OPN-375 186 mcg BID
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fluticasone Propionate
Intervention Description
OPN-375 186 μg BID, Delivered via exhalation delivery system
Primary Outcome Measure Information:
Title
Change From Visit 1 at End of Study in Bilateral Nasal Polyp Grade Using Endoscopic Video
Description
: 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
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Assessment for Safety by Recording Adverse Events and Adverse Events of Special Interests
Time Frame
24 Weeks, up to 30 days after last dose
Title
Assessment for Safety Through Nasal Examination
Description
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
Time Frame
24 Weeks, up to 30 days after last dose
Title
Assessment for Safety From Recording Vital Sign - Blood Pressure
Description
Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
Time Frame
Baseline, Week 12, Week 24
Title
Assessment for Safety From Recording Vital Sign - Pulse
Description
measure pulse in beats per minute (bpm)
Time Frame
Baseline, Week 12, Week 24
Title
Assessment for Safety From the Collection of Information for Concomitant Medications Usage
Time Frame
24 Weeks, up to 30 days after last dose
Title
Total Polyp Grading Score (Sum of Scores From Both Nasal Cavities)
Description
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
Time Frame
Week 24
Title
Number of Subjects With a Change of Greater Than or Equal to 1 Point in Bilateral Polyp Grade
Description
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
Time Frame
Week 24
Title
Number of Subjects With a Polyp Grade of 0 on at Least One Side of the Nose at Each Visit
Description
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
Time Frame
Week 24
Title
Sinonasal Outcome Test 22 (SNOT-22) Total Score
Description
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
Time Frame
Week 24
Title
Sniffin' Sticks N-butanol Test
Description
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.
Time Frame
Week 24
Title
Number of Participants With a PGIC Score of Minimally/Much/Very Much Improved
Description
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)
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Carothers
Organizational Affiliation
Optinose US Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
John Messina
Organizational Affiliation
Optinose US Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
University of Colorado SOM, Department of Otolaryngology
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Texas Health Science Center at Houston, McGovern Medical School, Dept. of Otolaryngology, Head and Neck Surgery
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
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Efficacy & Safety of OPN-375 Adults With Bilateral Nasal Polyps Using Nasoendoscopic Video
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