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

NCT ID: NCT03781804

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-27
• Study Completion Date: 2022-01-19

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 (CS) with or 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 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.

Conditions

Chronic Rhinosinusitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OPN-375 186 μg BID

OPN-375 186 μg BID x 24 Weeks

Group Type: ACTIVE_COMPARATOR

OPN-375

Intervention Type: DRUG

OPN-375, BID

OPN-375 372 μg BID

OPN-375 372 μg BID x 24 Weeks

Group Type: ACTIVE_COMPARATOR

OPN-375

Intervention Type: DRUG

OPN-375, BID

Placebo

Matching Placebo BID x 24 Weeks

Group Type: PLACEBO_COMPARATOR

OPN-375

Intervention Type: DRUG

OPN-375, BID

Interventions

OPN-375

OPN-375, BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Optinose US Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Carothers

Role: STUDY_DIRECTOR

Optinose US Inc.

John Messina

Role: STUDY_CHAIR

Optinose US Inc.

Locations

AZ Allergy & Immunology Research

Gilbert, Arizona, United States

Kern Research

Bakersfield, California, United States

Sacramento Ear, Nose & Throat Surgical and Medical Group Inc

Folsom, California, United States

Allergy & Asthma Specialists Medical Group

Huntington Beach, California, United States

Jonathan Corren, MD, Clinical Research Division

Los Angeles, California, United States

Sacramento Ear, Nose & Throat

Roseville, California, United States

UC Davis Medical Center

Sacramento, California, United States

Allergy and Asthma Associates of Santa Clara Valley

San Jose, California, United States

Breathe Clear Institute

Torrance, California, United States

Allergy & Asthma Clinical Research

Walnut Creek, California, United States

Colorado ENT & Allergy

Colorado Springs, Colorado, United States

Yale School of Medicine Section of Otolaryngology

New Haven, Connecticut, United States

Emory University MOT

Atlanta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

The University of Chicago

Chicago, Illinois, United States

Midwest Allergy Sinus Asthma

Normal, Illinois, United States

Advanced ENT and Allergy

New Albany, Indiana, United States

Iowa Head & Neck

Des Moines, Iowa, United States

Kentuckiana Ear Nose & Throat

Louisville, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

John Hopkins Hospital

Baltimore, Maryland, United States

Ear, Nose and Throat Associates at Greater Baltimore Medical Center

Towson, Maryland, United States

St. Cloud Ear, Nose & Throat

Saint Cloud, Minnesota, United States

University of Missouri, Dept of Otorlaryngology

Columbia, Missouri, United States

Asthma, Allergy, and Immunology Associates, PC

Lincoln, Nebraska, United States

Atlantic Research Center

Ocean City, New Jersey, United States

ENT and Allergy Associates

New Hyde Park, New York, United States

Mount Sinai Downtown Union Square

New York, New York, United States

Madison ENT and Facial Plastic Surgery

New York, New York, United States

Allergy Asthma & Immunology Relief of Charlotte

Charlotte, North Carolina, United States

Allergy Asthma & Clinical Research Center

Oklahoma City, Oklahoma, United States

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, United States

Northwest Research Center

Portland, Oregon, United States

Specialty Physician Associates

Bethlehem, Pennsylvania, United States

Hospital at the University of PA

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

National Allergy and Asthma Research

North Charleston, South Carolina, United States

Holston Medical Group

Kingsport, Tennessee, United States

University of TX Health Science Ctr at Houston

Houston, Texas, United States

STAAMP Research, LLC

San Antonio, Texas, United States

Intermountain Ear, Nose & Throat

Salt Lake City, Utah, United States

Chrysallis Clinical Research

St. George, Utah, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Bellingham Asthma, Allergy & Immunology Clinic

Bellingham, Washington, United States

Spokane ENT

Spokane Valley, Washington, United States

UMHAT - Kaspela EOOD

Plovdiv, , Bulgaria

MC Iskar

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment Serdika

Sofia, , Bulgaria

MC Pirogov

Sofia, , Bulgaria

The Military Medical Academy (MHAT)

Sofia, , Bulgaria

Мinistry of Interior - Medical Institute

Sofia, , Bulgaria

University of British Columbia and Providence Health Care

Vancouver, British Columbia, Canada

St. Joseph's Healthcare London

London, Ontario, Canada

CHU de Quebec, pavillon Hopital Saint- Sacrement

Québec, , Canada

Ltd Acad. Fridon Todua Medical Center

Tbilisi, , Georgia

Ltd Israel-Georgian Medical Research Clinic - Helsicore

Tbilisi, , Georgia

JSC Curatio

Tbilisi, , Georgia

Ltd Aversi Clinic

Tbilisi, , Georgia

Ltd Simon Khechinashvili University Hospital

Tbilisi, , Georgia

Jarosław Ślifirski Indywidualna Praktyka Lekarska

Kęty, Lesser Poland Voivodeship, Poland

Centrum Medyczne Biotamed

Wieliczka, Lesser Poland Voivodeship, Poland

Medicus Sp z o.o.

Wroclaw, Lower Silesian Voivodeship, Poland

Mini Clinic Paweł Białogłowski

Łańcut, Podkarpackie Voivodeship, Poland

Centrum Medyczne Angelius Provita

Katowice, Silesian Voivodeship, Poland

NZOZ Centrum Medyczne LiMED

Tarnowskie Góry, Silesian Voivodeship, Poland

NZOZ Imedica

Poznan, Wielkopolska, Poland

ReumaClinic

Bialystok, , Poland

Przychodnia "Narutowicza"

Inowrocław, , Poland

Centrum Medyczne All Med - Krakow

Krakow, , Poland

Medical Center Woś i Piwowarczyk

Krakow, , Poland

Centrum Alergologii

Lublin, , Poland

Centrum Medyczne Lucyna Andrazej Dymek - Strzelce Opolskie

Strzelce Opolskie, , Poland

NZOZ "Ignis" dr med. Alicja Łobińska

Świdnik, , Poland

NZOZ Przychodnia Medycyny Rodzinnej

Świętochłowice, , Poland

I.M. Sechenov First Moscow State Medical University-University Hospital No.1 - Ear, Nose, and Throat Clinic

Moscow, Moskovskaya Obl., Russia

Moscow Regional Scientific Research Clinical Institute n.a. M.F. Vladimirsky (MONIKI)

Moscow, Moskovskaya Obl., Russia

Saint-Petersburg State Medical University n.a. I.P. Pavlov

Saint Petersburg, Sankt-Peterburg, Russia

Smolensk, "Uromed"

Smolensk, Smolenskaya Obl, Russia

Yaroslavl Regional Clinical Hospital

Yaroslavl, Yaroslavskaya Obl., Russia

Central Clinical Hospital with Polyclinic" Office of Affairs of the President of the Russian Federation

Moscow, , Russia

Saint-Petersburg Institute of Ear, Nose, Throat, and Speech (The RSFSR Ministry of Health)

Saint Petersburg, , Russia

ONH Klinikun Skane Universitetssjukhuset (Lund - Oron- Nas- Och Halskliniken)

Lund, Skåne County, Sweden

Karolinska University Hospital

Stockholm, Stockholm County, Sweden

Helsingborg Hospital

Helsingborg, Sverige, Sweden

ONH Kliniken Sahlgrenska Universitetsynkhiset

Gothenburg, Vastra Gotaland Lan, Sweden

Sofiahemmet Hospital

Stockholm, , Sweden

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Darlington Memorial Hospital

Darlington, , United Kingdom

Lister Hospital

Stevenage, , United Kingdom

Stockport NHS Foundation Trust (Stepping Hill Hospital Base)

Stockport, , United Kingdom

Wrightington, Wigan and Leigh NHS Foundation Trust

Wigan, , United Kingdom

Countries

United States; Bulgaria; Canada; Georgia; Poland; Russia; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

OPN-FLU-CS-3205

Identifier Type: -

Identifier Source: org_study_id