Clinical trial NCT03960580: Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis
Lead sponsor: Optinose US Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 (CRS) without nasal polyps

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 the average morning 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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: 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
timeFrame: 4 Weeks
measure: Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses.
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).
timeFrame: Baseline, Week 4
measure: Time to First Acute Exacerbation of Chronic Sinusitis
timeFrame: 24 Weeks
measure: 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
timeFrame: 24 Weeks
measure: 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.
timeFrame: 8 weeks, 12 weeks.
measure: Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores
timeFrame: 8 Weeks; 12 Weeks
measure: Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores
timeFrame: Baseline, Week 8, Week 12
measure: Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores
timeFrame: Baseline, Week 8, Week 12
measure: Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores
timeFrame: Baseline, Week 8, Week 12
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score
timeFrame: Baseline, Week 24
measure: Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair
timeFrame: Baseline, Week 24
measure: 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.
timeFrame: Baseline, Week 24
measure: 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.
timeFrame: 24 weeks
measure: 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.
timeFrame: 24 weeks
measure: Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined
timeFrame: 24 Weeks
measure: Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score
timeFrame: Baseline, Week 24
measure: Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.
timeFrame: Baseline, Week 24
measure: Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined
timeFrame: 24 weeks
measure: 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
timeFrame: 24 Weeks
measure: Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 12 Weeks, 24 Weeks
measure: 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)
timeFrame: Week 4, Week 24
measure: Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)
timeFrame: 24 Weeks
measure: Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS).
timeFrame: 24 Weeks
measure: Change in the SF-36v2 Physical Component Score (PCS)
timeFrame: 24 Weeks
measure: 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)
timeFrame: 24 Weeks
measure: Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)
timeFrame: 24 Weeks
measure: Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™
timeFrame: 24 Weeks
measure: Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument
timeFrame: 24 Weeks
measure: Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument
timeFrame: 24 Weeks
measure: Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.
timeFrame: Baseline, Week 24
measure: Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery
timeFrame: Week 24
Other outcomes:
measure: Evaluation of Safety by Recording the Severity of Adverse Events (AEs)
timeFrame: 24 Weeks
measure: Evaluation of Safety-Nasal Examination
timeFrame: 24 Weeks
measure: Evaluation of Safety Measuring Vital Signs- Blood Pressure
timeFrame: 24 Weeks
measure: Evaluation of Safety Measuring Vital Signs- Pulse
timeFrame: 24 Weeks
measure: Evaluation of Safety Measuring Vital Signs- Weight
timeFrame: 24 Weeks
measure: Evaluation of Safety - Monitoring Concomitant Medication Usage
timeFrame: 24 Weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Folsom
country: United States
facility: Sacramento Ear, Nose & Throat Surgical and Medical Group Inc
state: California
city: La Mesa
country: United States
facility: BioSolutions Clinical Research Center
state: California
city: Los Angeles
country: United States
facility: Veterans Administration Greater Los Angeles Healthcare System
state: California
city: Roseville
country: United States
facility: Sacramento Ear, Nose & Throat Surgical and Medical Group
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates
state: Colorado
city: Largo
country: United States
facility: Sher Allergy Specialists
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: New Orleans
country: United States
facility: Best Clinical Trials
state: Louisiana
city: Columbia
country: United States
facility: University of Missouri, Dept of Otorlaryngology
state: Missouri
city: New York
country: United States
facility: Mount Sinai Downtown Union Square
state: New York
city: New York
country: United States
facility: Northwell Health at ENT and Allergy Associates
state: New York
city: Matthews
country: United States
facility: Charlotte Eye Ear Nose and Throat Assoc., PA
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Summerville
country: United States
facility: ENT & Allergy Partners, LLC
state: South Carolina
city: Houston
country: United States
facility: Pasha Snoring & Sinus Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Greenfield
country: United States
facility: Allergy, Asthma & Sinus Center, SC
state: Wisconsin
city: Bella Vista
country: Australia
facility: Otopure Pty Ltd
state: New South Wales
city: Brookvale
country: Australia
facility: Vale Medical Practice
state: New South Wales
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Browns Plains
country: Australia
facility: Browns Plains Family Practice
state: Queensland
city: Berwick
country: Australia
facility: Casey Superclinic
state: Victoria
city: Hawthorn East
country: Australia
facility: Camberwell Road Medical Practice
state: Victoria
city: Mirrabooka
country: Australia
facility: Mirrabooka Medical Centre
state: Western Australia
city: Spearwood
country: Australia
facility: Latitude Clinical Research
state: Western Australia
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Iskar EOOD
city: Sofia
country: Bulgaria
facility: MHAT Serdika EOOD
city: Sofia
country: Bulgaria
facility: MC N.I. Pirogov EOOD
city: Sofia
country: Bulgaria
facility: MHAT - Central Clinical Base Sofia Medical Institute Ministry of Interior
city: Sofia
country: Bulgaria
facility: MMA MHAT - Sofia
city: Sofia
country: Bulgaria
facility: DCC Convex EOOD
city: Stara Zagora
country: Bulgaria
facility: MHAT Trakiya EOOD
city: Varna
country: Bulgaria
facility: DCC "Mladost - M Varna" OOD
city: Benesov
country: Czechia
facility: Nemocnice Rudolfa a Stefanie Benesov, a.s., ORL oddeleni
city: Hradec Králové
country: Czechia
facility: FN Hradec Kralove, Klinika ORL
city: Mladá Boleslav
country: Czechia
facility: Pro-audio s.r.o.
city: Olomouc
country: Czechia
facility: MUDr. Pavel Navratil, ORL ambulance
city: Pardubice
country: Czechia
facility: Nemocnice Pardubického kraje - Pardubická nemocnice
city: Prague
country: Czechia
facility: AXON Clinical s.r.o.
city: Praha
country: Czechia
facility: VFN v Praze, oddeleni ORL
city: Tbilisi
country: Georgia
facility: Ltd Acad. Fridon Todua Medical Center- Research
city: Tbilisi
country: Georgia
facility: Ltd Israel-Georgian Medical Research Clinic - Helsicore
city: Tbilisi
country: Georgia
facility: JSC Curatio
city: Tbilisi
country: Georgia
facility: Ltd New Hospitals
city: Tbilisi
country: Georgia
facility: Ltd Simon Khechinashvili University Hospital
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi Heart Center
city: Tbilisi
country: Georgia
facility: Ltd Aversi Clinic
city: Tauranga
country: New Zealand
facility: P3 Research Tauranga Ltd.
state: Bay Of Plenty
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Hamilton
country: New Zealand
facility: Clinical Trials New Zealand
city: Wellington
country: New Zealand
facility: P3 Research Wellington Ltd.
city: Inowrocław
country: Poland
facility: Przychodnia "Narutowicza"
state: Kujawsko-Pomorskie
city: Kraków
country: Poland
facility: Centrum Medyczne All-Med
state: Malopolskie
city: Kęty
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska J. Slifirski
state: Malopolskie
city: Białystok
country: Poland
facility: ReumaClinic Gabinet Reumatologiczny
city: Białystok
country: Poland
facility: Centrum Medyczne MedSen Sp. z o.o.
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Kwiatowa
city: Gdynia
country: Poland
facility: Synexus Polska Sp. Z o. o., Oddzial w Gdyni ul. Luzycka 3c
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Lancut
country: Poland
facility: Mini-Clinic Paweł Białogłowski
city: Lublin
country: Poland
facility: Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
city: Strzelce Opolskie
country: Poland
facility: Centrum Medyczne Lucyna Andrzej Dymek S.C.
city: Swidnik
country: Poland
facility: NZOZ "Ignis" dr med. Alicja Lobinska
city: Tarnowskie Góry
country: Poland
facility: NZOZ Centrum Medyczne LiMED
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z.o.o. Oddzial w Warszawie
city: Wroclaw
country: Poland
facility: Synexus Polska Sp.zo.o. Oddział we Wrocławiu
city: Świętochłowice
country: Poland
facility: NZOZ Przychodnia Medycyny Rodzinnej
city: Braşov
country: Romania
facility: S.C. Centrul Medical Unirea S.R.L. Brasov
city: Bucharest
country: Romania
facility: SC Centrul Medical Unirea srl, Policlinica Primaverii
city: Bucharest
country: Romania
facility: S.C. Euroclinic Hospital S.A.
city: Cluj-Napoca
country: Romania
facility: Centrul Medical Cardiomed Cluj, Cabinet ORL
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Universitar CF Cluj-Napoca
city: Iaşi
country: Romania
facility: S.C. Centrul Medical Unirea S.R.L - IASI, Campus Medical Iasi - Cabinet ORL
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
state: Cadiz
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada Servicio de Otorrinolaringología
state: Madrid
city: Torrejon de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Barcelona
country: Spain
facility: Hospital Universitari Clinic de Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge, Servicio de Otorrinolaringología
city: Santiago De Compostela
country: Spain
facility: Consulta 164 Servicio ORL Hospital Clinico Universitario de Santiago de Compostela
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitario i Politecnic la Fe
city: Sutton-in-Ashfield
country: United Kingdom
facility: King's Mill Hospital
state: Nottinghamshire
Study officials:
affiliation: Optinose US Inc.
name: Jennifer Carothers
role: STUDY_DIRECTOR
affiliation: Optinose US Inc.
name: John Messina
role: STUDY_CHAIR
References: