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

September 12, 2023 updated by: Optinose US Inc.

A 24-Week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Rhinosinusitis With or Without the Presence of Nasal Polyps

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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

332

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Plovdiv, Bulgaria, 4002
        • UMHAT - Kaspela EOOD
      • Sofia, Bulgaria, 1000
        • MC Iskar
      • Sofia, Bulgaria, 1606
        • MC Pirogov
      • Sofia, Bulgaria, 1606
        • The Military Medical Academy (MHAT)
      • Sofia, Bulgaria, 1606
        • Мinistry of Interior - Medical Institute
      • Sofia, Bulgaria, 1303
        • Multiprofile Hospital for Active Treatment Serdika
      • Québec, Canada, G1S 4L8
        • CHU de Quebec, pavillon Hopital Saint- Sacrement
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • University of British Columbia and Providence Health Care
    • Ontario
      • London, Ontario, Canada, N6A 4V2
        • St. Joseph's Healthcare London
      • Tbilisi, Georgia, 0112
        • Ltd Acad. Fridon Todua Medical Center
      • Tbilisi, Georgia, 0112
        • Ltd Israel-Georgian Medical Research Clinic - Helsicore
      • Tbilisi, Georgia, 0114
        • JSC Curatio
      • Tbilisi, Georgia, 0160
        • LTD Aversi Clinic
      • Tbilisi, Georgia, 0179
        • LTD Simon Khechinashvili University Hospital
      • Białystok, Poland, 15-181
        • ReumaClinic
      • Inowrocław, Poland, 88-100
        • Przychodnia "Narutowicza"
      • Kraków, Poland, 31-572
        • Medical Center Woś i Piwowarczyk
      • Kraków, Poland, 30-033
        • Centrum Medyczne All Med - Krakow
      • Lublin, Poland, 20-552
        • Centrum Alergologii
      • Strzelce Opolskie, Poland, 47-100
        • Centrum Medyczne Lucyna Andrazej Dymek - Strzelce Opolskie
      • Świdnik, Poland, 21-040
        • NZOZ "Ignis" dr med. Alicja Łobińska
      • Świętochłowice, Poland, 41-600
        • NZOZ Przychodnia Medycyny Rodzinnej
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland, 50-224
        • Medicus Sp z o.o.
    • MA
      • Kęty, MA, Poland, 32-650
        • Jarosław Ślifirski Indywidualna Praktyka Lekarska
    • Malopolskie
      • Wieliczka, Malopolskie, Poland, 32-020
        • Centrum Medyczne Biotamed
    • PK
      • Łańcut, PK, Poland, 37-100
        • Mini Clinic Paweł Białogłowski
    • SL
      • Katowice, SL, Poland, 40-611
        • Centrum Medyczne Angelius Provita
      • Tarnowskie Góry, SL, Poland, 42-600
        • NZOZ Centrum Medyczne LiMED
    • Wielkopolska
      • Poznań, Wielkopolska, Poland, 60-537
        • NZOZ Imedica
      • Moscow, Russian Federation, 121359
        • Central Clinical Hospital with Polyclinic" Office of Affairs of the President of the Russian Federation
      • Saint Petersburg, Russian Federation, 190013
        • Saint-Petersburg Institute of Ear, Nose, Throat, and Speech (The RSFSR Ministry of Health)
    • Moskovskaya Obl.
      • Moscow, Moskovskaya Obl., Russian Federation, 119435
        • I.M. Sechenov First Moscow State Medical University-University Hospital No.1 - Ear, Nose, and Throat Clinic
      • Moscow, Moskovskaya Obl., Russian Federation, 129110
        • Moscow Regional Scientific Research Clinical Institute n.a. M.F. Vladimirsky (MONIKI)
    • Saint-Petersburg
      • Saint Petersburg, Saint-Petersburg, Russian Federation, 197022
        • Saint-Petersburg State Medical University n.a. I.P. Pavlov
    • Smolenskaya Obl
      • Smolensk, Smolenskaya Obl, Russian Federation, 214031
        • Smolensk, "Uromed"
    • Yaroslavskaya Obl.
      • Yaroslavl, Yaroslavskaya Obl., Russian Federation, 150062
        • Yaroslavl Regional Clinical Hospital
      • Stockholm, Sweden, 114 28
        • Sofiahemmet Hospital
    • Skane Lan
      • Lund, Skane Lan, Sweden, 222 41
        • ONH Klinikun Skane Universitetssjukhuset (Lund - Oron- Nas- Och Halskliniken)
    • Stockholms Lan
      • Stockholm, Stockholms Lan, Sweden, 171 76
        • Karolinska University Hospital
    • Sverige
      • Helsingborg, Sverige, Sweden, 25187
        • Helsingborg Hospital
    • Vastra Gotaland Lan
      • Gothenburg, Vastra Gotaland Lan, Sweden, 413 45
        • ONH Kliniken Sahlgrenska Universitetsynkhiset
      • Darlington, United Kingdom, DL3 6HX
        • Darlington Memorial Hospital
      • Stevenage, United Kingdom, SG1 4AB
        • Lister Hospital
      • Stockport, United Kingdom, SK2 7JE
        • Stockport NHS Foundation Trust (Stepping Hill Hospital Base)
      • Wigan, United Kingdom, WN1 2NN
        • Wrightington, Wigan and Leigh NHS Foundation Trust
    • Cf14 4xw
      • Cardiff, Cf14 4xw, United Kingdom
        • University Hospital of Wales
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • AZ Allergy & Immunology Research
    • California
      • Bakersfield, California, United States, 93301
        • Kern Research
      • Folsom, California, United States, 95630
        • Sacramento Ear, Nose & Throat Surgical and Medical Group Inc
      • Huntington Beach, California, United States, 92647
        • Allergy & Asthma Specialists Medical Group
      • Los Angeles, California, United States, 90025
        • Jonathan Corren, MD, Clinical Research Division
      • Roseville, California, United States, 95661
        • Sacramento Ear, Nose & Throat
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
      • San Jose, California, United States, 95117
        • Allergy and Asthma Associates of Santa Clara Valley
      • Torrance, California, United States, 90503
        • Breathe Clear Institute
      • Walnut Creek, California, United States, 94598
        • Allergy & Asthma Clinical Research
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Colorado ENT & Allergy
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale School of Medicine Section of Otolaryngology
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University MOT
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
      • Normal, Illinois, United States, 61761
        • Midwest Allergy Sinus Asthma
    • Indiana
      • New Albany, Indiana, United States, 47150
        • Advanced ENT and Allergy
    • Iowa
      • Des Moines, Iowa, United States, 50312-3505
        • Iowa Head & Neck
    • Kentucky
      • Louisville, Kentucky, United States, 40205
        • Kentuckiana Ear Nose & Throat
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • John Hopkins Hospital
      • Towson, Maryland, United States, 21204
        • Ear, Nose and Throat Associates at Greater Baltimore Medical Center
    • Minnesota
      • Saint Cloud, Minnesota, United States, 56303
        • St. Cloud Ear, Nose & Throat
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri, Dept of Otorlaryngology
    • Nebraska
      • Lincoln, Nebraska, United States, 68505
        • Asthma, Allergy, and Immunology Associates, PC
    • New Jersey
      • Ocean City, New Jersey, United States, 07712
        • Atlantic Research Center
    • New York
      • New Hyde Park, New York, United States, 11042
        • ENT and Allergy Associates
      • New York, New York, United States, 10003
        • Mount Sinai Downtown Union Square
      • New York, New York, United States, 10016
        • Madison ENT and Facial Plastic Surgery
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Allergy Asthma & Immunology Relief of Charlotte
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73120
        • Allergy Asthma & Clinical Research Center
      • Tulsa, Oklahoma, United States, 74136
        • Vital Prospects Clinical Research Institute, P.C.
    • Oregon
      • Portland, Oregon, United States, 97202
        • Northwest Research Center
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Specialty Physician Associates
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital at the University of PA
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • North Charleston, South Carolina, United States, 29420
        • National Allergy and Asthma Research
    • Tennessee
      • Kingsport, Tennessee, United States, 37660
        • Holston Medical Group
    • Texas
      • Houston, Texas, United States, 77030
        • University of TX Health Science Ctr at Houston
      • San Antonio, Texas, United States, 78229
        • STAAMP Research, LLC
    • Utah
      • Saint George, Utah, United States, 84790
        • Chrysallis Clinical Research
      • Salt Lake City, Utah, United States, 84102
        • Intermountain Ear, Nose & Throat
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Eastern Virginia Medical School
    • Washington
      • Bellingham, Washington, United States, 98225
        • Bellingham Asthma, Allergy & Immunology Clinic
      • Spokane Valley, Washington, United States, 99201
        • Spokane ENT

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: OPN-375 186 μg BID
OPN-375 186 μg BID x 24 Weeks
OPN-375, BID
Active Comparator: OPN-375 372 μg BID
OPN-375 372 μg BID x 24 Weeks
OPN-375, BID
Placebo Comparator: Placebo
Matching Placebo BID x 24 Weeks
OPN-375, BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4
Time Frame: 4 Weeks
Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
4 Weeks
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses
Time Frame: Baseline, Week 24
Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
Baseline, Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains
Time Frame: Week 24
The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. Each item is rated as follows: 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.
Week 24
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior)
Time Frame: Week 12
Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Week 12
Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores
Time Frame: 12 Weeks
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 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.
12 Weeks
Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores
Time Frame: 12 Weeks
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. The change reported in the results is calculated by subtracting the score reported at Baseline from the score reported at Visit 4 (Week 12).
12 Weeks
Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores
Time Frame: 12 Weeks
Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 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.
12 Weeks
Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores
Time Frame: 12 Weeks

Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 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 value reported in the results is calculated by subtracting the score reported by the patient at Baseline from the score reported by the patient at Visit 4 (Week 12).

12 Weeks
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations
Time Frame: 24 Weeks
Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for CRS with Nasal Polyps (NP) and without NP sub-groups and in patients with and without previous sinus surgery. Percent volume opacified can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefor, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
24 Weeks
Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score
Time Frame: Baseline, Week 24
Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.
Baseline, Week 24
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined
Time Frame: 24 Weeks

Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).

The values reported for this outcome are the change in total opacification of the left and right maxillary and ethmoid sinuses (Visit 6 [Wk 24] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid).

24 Weeks
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs
Time Frame: Week 24

Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).

Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at Baseline from the total score at Visit 6 (Wk 24).

Week 24
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment
Time Frame: Baseline, Week 24
Baseline, Week 24
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment
Time Frame: Baseline, Week 24
Baseline, Week 24
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations
Time Frame: 24 Weeks
Percent of sinus volume occupied by disease in the worst sinus between maxillary and ethmoid sinuses for the total population, chronic rhinosinusitis with nasal polyps (CRSwNP) subgroup, chronic rhinosinusitis without nasal polyps (CRSsNP) subgroup, patients with previous sinus surgery subgroup, and without previous surgery subgroup.
24 Weeks
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score
Time Frame: Baseline, Week 24

Zeinrich Modification of the Lund-Mackay Staging System:

Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 50.

Baseline, Week 24
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined
Time Frame: Baseline, Week 24

Zeinrich Modification of the Lund-Mackay Staging System:

Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results are determined by subtracting the total score at Baseline from the total score at Week 24.

Baseline, Week 24
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs
Time Frame: Baseline, Week 24

Zeinrich Modification of the Lund-Mackay Staging System:

Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% Each sinus pair (left and right side) listed below can achieve a total score of 0-10 (sum of score on each side). The values reported for this outcome calculated by subtracting the score at Baseline from the score at Visit 6 (Wk 24).

Baseline, Week 24
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations
Time Frame: Baseline, Week 24

Zeinrich Modification of the Lund-Mackay Staging System:

Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%

Baseline, Week 24
Time Comparison to First Acute Exacerbation of Chronic Sinusitis
Time Frame: 24 Weeks
Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment
24 Weeks
Percentage of Subjects Requiring Rescue Medication After Week 4
Time Frame: 8 Weeks
Recording of each dose of approved rescue medication after the Week 4 visit through Week 12
8 Weeks
Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)
Time Frame: 12 Weeks, 24 Weeks
The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 "component" scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome.
12 Weeks, 24 Weeks
Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)
Time Frame: Week 4, Week 24
Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse
Week 4, Week 24
Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
Time Frame: Week 24
The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome.
Week 24
Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS)
Time Frame: 24 Weeks
Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
24 Weeks
Change in the SF-36v2 Physical Composite Score (PCS)
Time Frame: 24 Weeks
Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
24 Weeks
Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)
Time Frame: 24 Weeks
The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate with a better health status, with 100 representing the highest level of functioning possible.
24 Weeks
Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
Time Frame: 24 Weeks
The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, with higher scores indicating a worse outcome.
24 Weeks
Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™
Time Frame: 24 Weeks
The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives to identify the odor accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposmia) as well as an index to detect malingering.
24 Weeks
Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS)
Time Frame: 24 Weeks
The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine).
24 Weeks
Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument
Time Frame: 24 Weeks
The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state).
24 Weeks
Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery
Time Frame: Baseline, Week 24
Percentage of subjects indicating that they are willing to consider Sinus Surgery
Baseline, Week 24
Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention
Time Frame: Baseline, Week 24
Percentage of Subjects who meet the minimal objective criteria for surgical intervention
Baseline, Week 24
Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery
Time Frame: Week 24
Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. The number of participants analyzed indicates the total number of participants for whom this analysis was completed.
Week 24
Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ).
Time Frame: 24 Weeks
The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. - Presenteeism can be converted to number of days of productive time lost per month, and when added to the number of lost days due to absenteeism provides an estimate of total productive work days lost.
24 Weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Safety-Nasal Examination
Time Frame: 24 Weeks
Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum.
24 Weeks
Evaluation of Safety - Monitoring Concomitant Medication Usage
Time Frame: 24 Weeks
Assessment for safety from the collection of information for concomitant medications usage
24 Weeks
Evaluation of Safety by Recording the Severity of Adverse Events (AEs)
Time Frame: 24 Weeks
Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe
24 Weeks
Evaluation of Safety Measuring Vital Signs- Blood Pressure
Time Frame: 24 Weeks
Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg)
24 Weeks
Evaluation of Safety Measuring Vital Signs- Pulse
Time Frame: 24 Weeks
Measure pulse in beats per minute (bpm)
24 Weeks
Evaluation of Safety Measuring Vital Signs- Weight
Time Frame: 24 Weeks
Assessment of safety from physical examination-weight measured in kg or lb
24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Jennifer Carothers, Optinose US Inc.
  • Study Chair: John Messina, Optinose US Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 27, 2018

Primary Completion (Actual)

January 19, 2022

Study Completion (Actual)

January 19, 2022

Study Registration Dates

First Submitted

December 18, 2018

First Submitted That Met QC Criteria

December 18, 2018

First Posted (Actual)

December 20, 2018

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 12, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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