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

NCT03960580 | Completed Phase 3 Results FDA Drug

• 1 other identifier: OPN-FLU-CS-3206
• Study Type: interventional
• Target: 223
• Locations: 10 countries
• Sites: 87

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

Conditions

Chronic Rhinosinusitis

Outcome Measures

Primary Outcomes (2)

• 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

  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 (APOV) in the Ethmoid and Maxillary Sinuses.

  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 Outcomes (32)

• Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).

  Baseline, Week 4

• Time to First Acute Exacerbation of Chronic Sinusitis

  24 Weeks

• 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

  24 Weeks

• 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.

  8 weeks, 12 weeks.

• Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores

  8 Weeks; 12 Weeks

Other Outcomes (6)

• Evaluation of Safety by Recording the Severity of Adverse Events (AEs)

  24 Weeks

• Evaluation of Safety-Nasal Examination

  24 Weeks

• Evaluation of Safety Measuring Vital Signs- Blood Pressure

  24 Weeks

Study Arms (3)

OPN-375 186 μg BID

ACTIVE COMPARATOR

OPN-375 186 μg BID x 24 Weeks

Drug: OPN-375

OPN-375 372 μg BID

ACTIVE COMPARATOR

OPN-375 372 μg BID x 24 Weeks

Drug: OPN-375

Placebo

PLACEBO COMPARATOR

Matching Placebo BID x 24 Weeks

Drug: OPN-375

Interventions

OPN-375 DRUG

OPN-375, BID

OPN-375 186 μg BID; OPN-375 372 μg BID; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men or women aged 18 years and older at baseline visit
• women of child bearing potential must be abstinent, or if sexually active,
• 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
• be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
• be postmenopausal (amenorrhea for at least 1 year)
• women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)
• 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
• endoscopic evidence of nasal mucosal disease, with edema or purulent discharge; or polyps/polypoid tissue \<Grade 1 in middle meatus, bilaterally
• 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)
• baseline CT scan must show a combined ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus
• 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

You may not qualify if:

• women who are pregnant or lactating
• inability to have each nasal cavity examined for any reason, including nasal septum deviation
• inability to achieve bilateral nasal airflow
• is currently taking XHANCE®
• have previously used XHANCE® for more than 1 month and did not achieve an adequate symptomatic response
• the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan
• history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery
• 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)
• have a paranasal sinus or nasal tumor
• 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
• have a nasal septum perforation
• have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)
• have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy
• have current, ongoing rhinitis medicamentosa (rebound rhinitis)
• have significant oral structural abnormalities (eg, a cleft palate)

Sponsors & Collaborators

• Optinose US Inc.: lead

Study Sites (87)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Sacramento Ear, Nose & Throat Surgical and Medical Group Inc

Folsom, California, 95630, United States

Location

BioSolutions Clinical Research Center

La Mesa, California, 91942-3007, United States

Location

Veterans Administration Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Sacramento Ear, Nose & Throat Surgical and Medical Group

Roseville, California, 95661, United States

Location

Asthma and Allergy Associates

Colorado Springs, Colorado, 80907, United States

Location

Sher Allergy Specialists

Largo, Florida, 33778, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Treasure Valley Medical Research

Boise, Idaho, 83706, United States

Location

Best Clinical Trials

New Orleans, Louisiana, 70115, United States

Location

University of Missouri, Dept of Otorlaryngology

Columbia, Missouri, 65212, United States

Location

Mount Sinai Downtown Union Square

New York, New York, 10003, United States

Location

Northwell Health at ENT and Allergy Associates

New York, New York, 10016, United States

Location

Charlotte Eye Ear Nose and Throat Assoc., PA

Matthews, North Carolina, 28105, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15219, United States

Location

ENT & Allergy Partners, LLC

Summerville, South Carolina, 29486, United States

Location

Pasha Snoring & Sinus Center

Houston, Texas, 77082, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Allergy, Asthma & Sinus Center, SC

Greenfield, Wisconsin, 53228, United States

Location

Otopure Pty Ltd

Bella Vista, New South Wales, 2153, Australia

Location

Vale Medical Practice

Brookvale, New South Wales, 2100, Australia

Location

Australian Clinical Research Network

Maroubra, New South Wales, 2035, Australia

Location

Browns Plains Family Practice

Browns Plains, Queensland, 4118, Australia

Location

Casey Superclinic

Berwick, Victoria, 3806, Australia

Location

Camberwell Road Medical Practice

Hawthorn East, Victoria, 3123, Australia

Location

Mirrabooka Medical Centre

Mirrabooka, Western Australia, 6061, Australia

Location

Latitude Clinical Research

Spearwood, Western Australia, 6163, Australia

Location

UMHAT Kaspela EOOD

Plovdiv, 4002, Bulgaria

Location

Medical Center Iskar EOOD

Sofia, 1000, Bulgaria

Location

MHAT Serdika EOOD

Sofia, 1303, Bulgaria

Location

MC N.I. Pirogov EOOD

Sofia, 1606, Bulgaria

Location

MHAT - Central Clinical Base Sofia Medical Institute Ministry of Interior

Sofia, 1606, Bulgaria

Location

MMA MHAT - Sofia

Sofia, 1606, Bulgaria

Location

DCC Convex EOOD

Sofia, 1680, Bulgaria

Location

MHAT Trakiya EOOD

Stara Zagora, 6000, Bulgaria

Location

DCC "Mladost - M Varna" OOD

Varna, 9020, Bulgaria

Location

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

Benešov, 256 01, Czechia

Location

FN Hradec Kralove, Klinika ORL

Hradec Králové, 500 05, Czechia

Location

Pro-audio s.r.o.

Mladá Boleslav, 293 01, Czechia

Location

MUDr. Pavel Navratil, ORL ambulance

Olomouc, 779 00, Czechia

Location

Nemocnice Pardubického kraje - Pardubická nemocnice

Pardubice, 532 03, Czechia

Location

VFN v Praze, oddeleni ORL

Prague, 128 08, Czechia

Location

AXON Clinical s.r.o.

Prague, 150 00, Czechia

Location

Ltd Acad. Fridon Todua Medical Center- Research

Tbilisi, 0112, Georgia

Location

Ltd Israel-Georgian Medical Research Clinic - Helsicore

Tbilisi, 0112, Georgia

Location

JSC Curatio

Tbilisi, 0114, Georgia

Location

Ltd New Hospitals

Tbilisi, 0114, Georgia

Location

Ltd Simon Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

Ltd Tbilisi Heart Center

Tbilisi, 0186, Georgia

Location

Ltd Aversi Clinic

Tbilisi, 1060, Georgia

Location

P3 Research Tauranga Ltd.

Tauranga, Bay of Plenty, 3110, New Zealand

Location

Optimal Clinical Trials

Auckland, 1010, New Zealand

Location

Clinical Trials New Zealand

Hamilton, 3206, New Zealand

Location

P3 Research Wellington Ltd.

Wellington, 6021, New Zealand

Location

Przychodnia "Narutowicza"

Inowrocław, Kuyavian-Pomeranian Voivodeship, 88-100, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska J. Slifirski

Kęty, Lesser Poland Voivodeship, 32-650, Poland

Location

Centrum Medyczne All-Med

Krakow, Lesser Poland Voivodeship, 30-033, Poland

Location

ReumaClinic Gabinet Reumatologiczny

Bialystok, 15-166, Poland

Location

Centrum Medyczne MedSen Sp. z o.o.

Bialystok, 15-691, Poland

Location

Centrum Medyczne Kwiatowa

Bydgoszcz, 85-047, Poland

Location

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

Gdynia, 81-537, Poland

Location

Centrum Medyczne Angelius Provita

Katowice, 40-611, Poland

Location

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

Lublin, 20-552, Poland

Location

Centrum Medyczne Lucyna Andrzej Dymek S.C.

Strzelce Opolskie, 47-100, Poland

Location

NZOZ "Ignis" dr med. Alicja Lobinska

Świdnik, 21-040, Poland

Location

NZOZ Przychodnia Medycyny Rodzinnej

Świętochłowice, 41-600, Poland

Location

NZOZ Centrum Medyczne LiMED

Tarnowskie Góry, 42-600, Poland

Location

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

Warsaw, 01-192, Poland

Location

Synexus Polska Sp.zo.o. Oddział we Wrocławiu

Wroclaw, 50-381, Poland

Location

Mini-Clinic Paweł Białogłowski

Łańcut, 37-100, Poland

Location

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

Brasov, 500091, Romania

Location

SC Centrul Medical Unirea srl, Policlinica Primaverii

Bucharest, 011858, Romania

Location

S.C. Euroclinic Hospital S.A.

Bucharest, 014461, Romania

Location

Centrul Medical Cardiomed Cluj, Cabinet ORL

Cluj-Napoca, 400015, Romania

Location

Spitalul Clinic Universitar CF Cluj-Napoca

Cluj-Napoca, 400015, Romania

Location

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

Iași, 700023, Romania

Location

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Cadiz, 11407, Spain

Location

Hospital Universitario de Fuenlabrada Servicio de Otorrinolaringología

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid, 28850, Spain

Location

Centro Médico Teknon

Barcelona, 08022, Spain

Location

Hospital Universitari Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari de Bellvitge, Servicio de Otorrinolaringología

L'Hospitalet de Llobregat, 08907, Spain

Location

Consulta 164 Servicio ORL Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario i Politecnic la Fe

Valencia, 46026, Spain

Location

King's Mill Hospital

Sutton in Ashfield, Nottinghamshire, NG17 4JL, United Kingdom

Location

Results Point of Contact

• Title: John Messina, PharmD, SVP of Clinical Research & Medical Affairs
• Organization: OptiNose

john.messina@optinose.com

265-521-0565

Study Officials

• Jennifer Carothers

  Optinose US Inc.

  STUDY DIRECTOR

• John Messina

  Optinose US Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 23, 2019
• Study Start: June 6, 2019
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: December 21, 2023
• Results First Posted: December 21, 2023

Record last verified: 2023-12

Locations

PL (16); NZ (4); RO (6); GB (1); BU (9); AU (8); ES (9); US (20); CZ (7); GE (7)