Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps

NCT ID: NCT03960580

Last Updated: 2023-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 223 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-06
• Study Completion Date: 2022-05-04

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.

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

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.

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.

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

• 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

University of Alabama at Birmingham

Birmingham, Alabama, United States

Sacramento Ear, Nose & Throat Surgical and Medical Group Inc

Folsom, California, United States

BioSolutions Clinical Research Center

La Mesa, California, United States

Veterans Administration Greater Los Angeles Healthcare System

Los Angeles, California, United States

Sacramento Ear, Nose & Throat Surgical and Medical Group

Roseville, California, United States

Asthma and Allergy Associates

Colorado Springs, Colorado, United States

Sher Allergy Specialists

Largo, Florida, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

Treasure Valley Medical Research

Boise, Idaho, United States

Best Clinical Trials

New Orleans, Louisiana, United States

University of Missouri, Dept of Otorlaryngology

Columbia, Missouri, United States

Mount Sinai Downtown Union Square

New York, New York, United States

Northwell Health at ENT and Allergy Associates

New York, New York, United States

Charlotte Eye Ear Nose and Throat Assoc., PA

Matthews, North Carolina, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

ENT & Allergy Partners, LLC

Summerville, South Carolina, United States

Pasha Snoring & Sinus Center

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Allergy, Asthma & Sinus Center, SC

Greenfield, Wisconsin, United States

Otopure Pty Ltd

Bella Vista, New South Wales, Australia

Vale Medical Practice

Brookvale, New South Wales, Australia

Australian Clinical Research Network

Maroubra, New South Wales, Australia

Browns Plains Family Practice

Browns Plains, Queensland, Australia

Casey Superclinic

Berwick, Victoria, Australia

Camberwell Road Medical Practice

Hawthorn East, Victoria, Australia

Mirrabooka Medical Centre

Mirrabooka, Western Australia, Australia

Latitude Clinical Research

Spearwood, Western Australia, Australia

UMHAT Kaspela EOOD

Plovdiv, , Bulgaria

Medical Center Iskar EOOD

Sofia, , Bulgaria

MHAT Serdika EOOD

Sofia, , Bulgaria

MC N.I. Pirogov EOOD

Sofia, , Bulgaria

MHAT - Central Clinical Base Sofia Medical Institute Ministry of Interior

Sofia, , Bulgaria

MMA MHAT - Sofia

Sofia, , Bulgaria

DCC Convex EOOD

Sofia, , Bulgaria

MHAT Trakiya EOOD

Stara Zagora, , Bulgaria

DCC "Mladost - M Varna" OOD

Varna, , Bulgaria

Nemocnice Rudolfa a Stefanie Benesov, a.s., ORL oddeleni

Benešov, , Czechia

FN Hradec Kralove, Klinika ORL

Hradec Králové, , Czechia

Pro-audio s.r.o.

Mladá Boleslav, , Czechia

MUDr. Pavel Navratil, ORL ambulance

Olomouc, , Czechia

Nemocnice Pardubického kraje - Pardubická nemocnice

Pardubice, , Czechia

VFN v Praze, oddeleni ORL

Prague, , Czechia

AXON Clinical s.r.o.

Prague, , Czechia

Ltd Acad. Fridon Todua Medical Center- Research

Tbilisi, , Georgia

Ltd Israel-Georgian Medical Research Clinic - Helsicore

Tbilisi, , Georgia

JSC Curatio

Tbilisi, , Georgia

Ltd New Hospitals

Tbilisi, , Georgia

Ltd Simon Khechinashvili University Hospital

Tbilisi, , Georgia

Ltd Tbilisi Heart Center

Tbilisi, , Georgia

Ltd Aversi Clinic

Tbilisi, , Georgia

P3 Research Tauranga Ltd.

Tauranga, Bay of Plenty, New Zealand

Optimal Clinical Trials

Auckland, , New Zealand

Clinical Trials New Zealand

Hamilton, , New Zealand

P3 Research Wellington Ltd.

Wellington, , New Zealand

Przychodnia "Narutowicza"

Inowrocław, Kuyavian-Pomeranian Voivodeship, Poland

Indywidualna Specjalistyczna Praktyka Lekarska J. Slifirski

Kęty, Lesser Poland Voivodeship, Poland

Centrum Medyczne All-Med

Krakow, Lesser Poland Voivodeship, Poland

ReumaClinic Gabinet Reumatologiczny

Bialystok, , Poland

Centrum Medyczne MedSen Sp. z o.o.

Bialystok, , Poland

Centrum Medyczne Kwiatowa

Bydgoszcz, , Poland

Synexus Polska Sp. Z o. o., Oddzial w Gdyni ul. Luzycka 3c

Gdynia, , Poland

Centrum Medyczne Angelius Provita

Katowice, , Poland

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

Lublin, , Poland

Centrum Medyczne Lucyna Andrzej Dymek S.C.

Strzelce Opolskie, , Poland

NZOZ "Ignis" dr med. Alicja Lobinska

Świdnik, , Poland

NZOZ Przychodnia Medycyny Rodzinnej

Świętochłowice, , Poland

NZOZ Centrum Medyczne LiMED

Tarnowskie Góry, , Poland

Synexus Polska Sp. z.o.o. Oddzial w Warszawie

Warsaw, , Poland

Synexus Polska Sp.zo.o. Oddział we Wrocławiu

Wroclaw, , Poland

Mini-Clinic Paweł Białogłowski

Łańcut, , Poland

S.C. Centrul Medical Unirea S.R.L. Brasov

Brasov, , Romania

SC Centrul Medical Unirea srl, Policlinica Primaverii

Bucharest, , Romania

S.C. Euroclinic Hospital S.A.

Bucharest, , Romania

Centrul Medical Cardiomed Cluj, Cabinet ORL

Cluj-Napoca, , Romania

Spitalul Clinic Universitar CF Cluj-Napoca

Cluj-Napoca, , Romania

S.C. Centrul Medical Unirea S.R.L - IASI, Campus Medical Iasi - Cabinet ORL

Iași, , Romania

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Cadiz, Spain

Hospital Universitario de Fuenlabrada Servicio de Otorrinolaringología

Fuenlabrada, Madrid, Spain

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid, Spain

Centro Médico Teknon

Barcelona, , Spain

Hospital Universitari Clinic de Barcelona

Barcelona, , Spain

Hospital Universitari de Bellvitge, Servicio de Otorrinolaringología

L'Hospitalet de Llobregat, , Spain

Consulta 164 Servicio ORL Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario i Politecnic la Fe

Valencia, , Spain

King's Mill Hospital

Sutton in Ashfield, Nottinghamshire, United Kingdom

Countries

United States; Australia; Bulgaria; Czechia; Georgia; New Zealand; Poland; Romania; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

OPN-FLU-CS-3206

Identifier Type: -

Identifier Source: org_study_id