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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03960580




Registration number
NCT03960580
Ethics application status
Date submitted
20/05/2019
Date registered
23/05/2019
Date last updated
21/12/2023

Titles & IDs
Public title
Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps
Scientific title
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 Without the Presence of Nasal Polyps
Secondary ID [1] 0 0
OPN-FLU-CS-3206
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - OPN-375

Active comparator: OPN-375 186 µg BID - OPN-375 186 µg BID x 24 Weeks

Active comparator: OPN-375 372 µg BID - OPN-375 372 µg BID x 24 Weeks

Placebo comparator: Placebo - Matching Placebo BID x 24 Weeks


Treatment: Drugs: OPN-375
OPN-375, BID
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
4 Weeks
Primary outcome [2] 0 0
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses.
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).
Timepoint [1] 0 0
Baseline, Week 4
Secondary outcome [2] 0 0
Time to First Acute Exacerbation of Chronic Sinusitis
Timepoint [2] 0 0
24 Weeks
Secondary outcome [3] 0 0
Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains
Timepoint [3] 0 0
24 Weeks
Secondary outcome [4] 0 0
Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery.
Timepoint [4] 0 0
8 weeks, 12 weeks.
Secondary outcome [5] 0 0
Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores
Timepoint [5] 0 0
8 Weeks; 12 Weeks
Secondary outcome [6] 0 0
Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores
Timepoint [6] 0 0
Baseline, Week 8, Week 12
Secondary outcome [7] 0 0
Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores
Timepoint [7] 0 0
Baseline, Week 8, Week 12
Secondary outcome [8] 0 0
Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores
Timepoint [8] 0 0
Baseline, Week 8, Week 12
Secondary outcome [9] 0 0
Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment.
Timepoint [12] 0 0
Baseline, Week 24
Secondary outcome [13] 0 0
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment.
Timepoint [13] 0 0
24 weeks
Secondary outcome [14] 0 0
Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment.
Timepoint [14] 0 0
24 weeks
Secondary outcome [15] 0 0
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined
Timepoint [15] 0 0
24 Weeks
Secondary outcome [16] 0 0
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined
Timepoint [18] 0 0
24 weeks
Secondary outcome [19] 0 0
Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations
Timepoint [19] 0 0
24 Weeks
Secondary outcome [20] 0 0
Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)
Timepoint [20] 0 0
12 Weeks, 24 Weeks
Secondary outcome [21] 0 0
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)
Timepoint [21] 0 0
Week 4, Week 24
Secondary outcome [22] 0 0
Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)
Timepoint [22] 0 0
24 Weeks
Secondary outcome [23] 0 0
Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS).
Timepoint [23] 0 0
24 Weeks
Secondary outcome [24] 0 0
Change in the SF-36v2 Physical Component Score (PCS)
Timepoint [24] 0 0
24 Weeks
Secondary outcome [25] 0 0
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)
Timepoint [25] 0 0
24 Weeks
Secondary outcome [26] 0 0
Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
Timepoint [26] 0 0
24 Weeks
Secondary outcome [27] 0 0
Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™
Timepoint [27] 0 0
24 Weeks
Secondary outcome [28] 0 0
Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument
Timepoint [28] 0 0
24 Weeks
Secondary outcome [29] 0 0
Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument
Timepoint [29] 0 0
24 Weeks
Secondary outcome [30] 0 0
Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24
Timepoint [30] 0 0
Baseline, Week 24
Secondary outcome [31] 0 0
Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.
Timepoint [31] 0 0
Baseline, Week 24
Secondary outcome [32] 0 0
Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery
Timepoint [32] 0 0
Week 24

Eligibility
Key inclusion criteria
1. men or women aged 18 years and older at baseline visit
2. women of child bearing 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 sinusitis 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 or purulent discharge; or polyps/polypoid tissue <Grade 1 in middle meatus, bilaterally
6. must have confirmatory evidence via a computed tomography(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 correctly; all subjects will be required to demonstrate correct use with the practice exhalation delivery system (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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. women who are pregnant or lactating
2. inability to have each nasal cavity examined for any reason, including nasal septum deviation
3. 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 polyp grade =1 (polyp that is free on 5 sides and has a stalk) on either side of the nose 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 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 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 chronic sinusitis 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, intraarticular, 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 elevation on any form of steroid therapy
28. history or current diagnosis of the presence (in either eye) of a subcapsular cataract
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) inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole)
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 care professional is not exclusionary.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/05/2022
Sample size
Target
Accrual to date
Final
223
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Otopure Pty Ltd - Bella Vista
Recruitment hospital [2] 0 0
Vale Medical Practice - Brookvale
Recruitment hospital [3] 0 0
Australian Clinical Research Network - Maroubra
Recruitment hospital [4] 0 0
Browns Plains Family Practice - Browns Plains
Recruitment hospital [5] 0 0
Casey Superclinic - Berwick
Recruitment hospital [6] 0 0
Camberwell Road Medical Practice - Hawthorn East
Recruitment hospital [7] 0 0
Mirrabooka Medical Centre - Mirrabooka
Recruitment hospital [8] 0 0
Latitude Clinical Research - Spearwood
Recruitment postcode(s) [1] 0 0
2153 - Bella Vista
Recruitment postcode(s) [2] 0 0
2100 - Brookvale
Recruitment postcode(s) [3] 0 0
2035 - Maroubra
Recruitment postcode(s) [4] 0 0
4118 - Browns Plains
Recruitment postcode(s) [5] 0 0
3806 - Berwick
Recruitment postcode(s) [6] 0 0
3123 - Hawthorn East
Recruitment postcode(s) [7] 0 0
6061 - Mirrabooka
Recruitment postcode(s) [8] 0 0
6163 - Spearwood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Stara Zagora
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Varna
Country [20] 0 0
Czechia
State/province [20] 0 0
Benesov
Country [21] 0 0
Czechia
State/province [21] 0 0
Hradec Králové
Country [22] 0 0
Czechia
State/province [22] 0 0
Mladá Boleslav
Country [23] 0 0
Czechia
State/province [23] 0 0
Olomouc
Country [24] 0 0
Czechia
State/province [24] 0 0
Pardubice
Country [25] 0 0
Czechia
State/province [25] 0 0
Prague
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha
Country [27] 0 0
Georgia
State/province [27] 0 0
Tbilisi
Country [28] 0 0
New Zealand
State/province [28] 0 0
Bay Of Plenty
Country [29] 0 0
New Zealand
State/province [29] 0 0
Auckland
Country [30] 0 0
New Zealand
State/province [30] 0 0
Hamilton
Country [31] 0 0
New Zealand
State/province [31] 0 0
Wellington
Country [32] 0 0
Poland
State/province [32] 0 0
Kujawsko-Pomorskie
Country [33] 0 0
Poland
State/province [33] 0 0
Malopolskie
Country [34] 0 0
Poland
State/province [34] 0 0
Bialystok
Country [35] 0 0
Poland
State/province [35] 0 0
Bydgoszcz
Country [36] 0 0
Poland
State/province [36] 0 0
Gdynia
Country [37] 0 0
Poland
State/province [37] 0 0
Katowice
Country [38] 0 0
Poland
State/province [38] 0 0
Lancut
Country [39] 0 0
Poland
State/province [39] 0 0
Lublin
Country [40] 0 0
Poland
State/province [40] 0 0
Strzelce Opolskie
Country [41] 0 0
Poland
State/province [41] 0 0
Swidnik
Country [42] 0 0
Poland
State/province [42] 0 0
Tarnowskie Góry
Country [43] 0 0
Poland
State/province [43] 0 0
Warszawa
Country [44] 0 0
Poland
State/province [44] 0 0
Wroclaw
Country [45] 0 0
Poland
State/province [45] 0 0
Swietochlowice
Country [46] 0 0
Romania
State/province [46] 0 0
Brasov
Country [47] 0 0
Romania
State/province [47] 0 0
Bucharest
Country [48] 0 0
Romania
State/province [48] 0 0
Cluj-Napoca
Country [49] 0 0
Romania
State/province [49] 0 0
Iasi
Country [50] 0 0
Spain
State/province [50] 0 0
Cadiz
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
L'Hospitalet De Llobregat
Country [54] 0 0
Spain
State/province [54] 0 0
Santiago De Compostela
Country [55] 0 0
Spain
State/province [55] 0 0
Seville
Country [56] 0 0
Spain
State/province [56] 0 0
Valencia
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Nottinghamshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Optinose US Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jennifer Carothers
Address 0 0
Optinose US Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03960580