Chronic Rhinosinusitis Without Nasal PolypsPhase 3Re-Open 3NCT06850805
Efficacy and Safety of 186 mcg of OPN-375 Nasal Spray Twice a Day (BID) in Adolescents With Chronic Rhinosinusitis Without Nasal Polyps
A Phase 3 study testing OPN-375 in people with Chronic Rhinosinusitis Without Nasal Polyps, run by Optinose US Inc. at 24 sites in United States.
Trial summary
This is a 12-Week randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating the efficacy and safety of intranasal administration of 186 µg of OPN-375 twice a day (BID) in adolescent subjects with chronic rhinosinusitis without nasal polyps. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Chronic Rhinosinusitis Without Nasal Polyps
- What is being tested?
- OPN-375
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 24 sitesUnited States
- Study dates
- 28 Jul 2025to 31 Oct 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening)
- Female subjects, if sexually active, must:
- be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., 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 abstinent.
- Females of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening).
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- Must have a history of CRS 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
- Must have endoscopic evidence of nasal mucosal disease, with edema, or purulent discharge bilaterally, or presence of bilateral disease on a prior computed tomography (CT) scan performed within 14 days of Visit 1.
- 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.
- 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.
- Must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization.
- Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2021 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening), and are expected to remain on it throughout the study. Subjects receiving inhaled fluticasone alone or in combination may not participate in the PK sub-study.
- 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.
- Must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma) at the screening visit
- If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to Visit 1 (Screening), and agree to not change the dose of these medications until after Week 4 of the study.
- 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).
- Must be capable, in the opinion of the investigator, of providing assent and parent or guardian must provide 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 that they are willing to participate in the study.
Who cannot join
- Females 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.
- History of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery.
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- 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 a nasal polyp score of grade 1 or greater in either nostril 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).
- Have a diagnosis of cystic fibrosis.
- History of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).
- 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. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.
- Planned sinonasal surgery during the period of the study.
- Allergy, hypersensitivity, or contraindication to corticosteroids or steroids.
- Has used oral steroids in the past for treatment of CS and did not experience any relief of symptoms.
- Has a steroid eluting sinus stent still in place within 30 days of Visit 1.
- Allergy or hypersensitivity to any excipients in study drug.
- Exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD.
- Have nasal or oral candidiasis.
- History or current diagnosis of any form of glaucoma or ocular hypertension.
- History of IOP elevation on any form of steroid therapy.
- History or current diagnosis of the presence (in either eye) of a cataract unless both natural intraocular lenses have been removed.
- History of immunodeficiency of any etiology (including poor nutrition) that would be anticipated to affect the likelihood of benefit or harm from the therapeutic intervention.
- 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.
- Have a positive drug screen or a 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.
- Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening).
- Have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), benralizumab (Fasenra™), Tezepelumab-ekko (Tezspire®) or any other immune-modifying monoclonal antibody within 6 months of Visit 1 (Screening).
- Is using strong cytochrome P450 3A4 (CYP3A4) inhibitor (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole, cobicistat).
- Has a parent, guardian or caregiver who 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.
- Patients who report unexplained worsening of vision within the past 3 months.
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Amy Manley contact
24 sites in 1 country
United States24 sites, 23 recruiting
- Not yet recruiting
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
India Taliaferro, 404-785-0534, India.Taliaferro@choa.org
Lori Gentile, MD
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Paul Hynes, 720-777-3570, paul.hynes@cuanschutz.edu
Sarah Gitomer, MD
- Recruiting
Orion Clinical Research
Austin, Texas, 78759
Stephanie Nunnelee, 512-492-3799, sfnunnelee@orionclinicalresearch.com
William Howland, III, MD
- Recruiting
Colorado ENT & Allergy
Colorado Springs, Colorado, 80909
Monica Davis, 719-867-7804, mdavis@coloradoent.com
Bryan Davis, MD
- Recruiting
University of Missouri Medical Center
Columbia, Missouri, 65212
Rebecca Schneider, 573-882-2549, schniederri@health.missouri.edu
Christine Franzese, MD
- Withdrawn
San Tan Allergy & Asthma
Gilbert, Arizona, 85214
- Not yet recruiting
North Alabama ENT
Huntsville, Alabama, 35801
Brittany Cope, 256-322-1553, bcope@medovationresearch.com
Jasper Castillo, MD
- Not yet recruiting
Childrens Hospital of Los Angeles
Los Angeles, California, 90027
Beth (Osterbauer) Giannascoli, 323-361-3539, bosterbauer@chla.usc.edu
Elisabeth Ference, MD
- Recruiting
Kentuckiana ENT
Louisville, Kentucky, 40205
Wendi Miller, 502-894-8441, wmiller@kentuckianaent.com
Thomas Higgins, MD
- Recruiting
EVMS at Old Dominion University
Norfolk, Virginia, 23507
Laura Stone, 757-388-6238, stonelj@evms.edu
Kent Lam, MD
- Recruiting
Charleston ENT & Allergy
North Charleston, South Carolina, 29414
Britney Ragoonath, 843-654-8884, bragoonath@charlestonent.com
Thomas Murphy, MD
- Recruiting
Allergy, Asthma and Clinical Research Center
Oklahoma City, Oklahoma, 73120
Nasir Ali, MD, 405-286-9431, ali@mtarpay.com
Martha Tarpay, MD
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
Jenny Vo, 714-509-4254, jenny.vo@choc.org
Jay Bhatt, MD
- Recruiting
Carolina ENT Clinic/CENTRI Inc.
Orangeburg, South Carolina, 29118
Simone Ansley, 803-536-5511, sansley700@gmail.com
John Ansley, MD
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Paul Allen, 585-275-1186, paul_allen@urmc.rochester.edu
Li-Xing Man, MD
- Recruiting
DaVinci Research, LLC
Sacramento, California, 95661
Rose Khalatyan, 916-531-2788, rkhalatyan@davinciresearch.net
Randall Ow, MD
- Recruiting
University of Utah
Salt Lake City, Utah, 84112
WIlson CHen, 801-585-4327, u0661901@umail.utah.edu
Jill Jeffe, MD
- Recruiting
STAAMP Research
San Antonio, Texas, 78229
Dario Rocha, 210-614-6673, dario@staampresearch.com
Erika Gonzalez, MD
- Recruiting
Alamo ENT Associates
San Antonio, Texas, 78258
Maxine Mata, 210-545-0404, m.mata@alamoent.com
Jeffrey Rosenbloom, MD
- Not yet recruiting
Rady Childrens Hospital San Diego
San Diego, California, 92123
Sasha Shenk, 858-966-1700 ext. 224190, sshenk@rchsd.org
Vijay Patel, MD
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Alaine Nixon, 217-545-8065, anixon45@siumed.edu
Dana Crosby, MD
- Recruiting
Breathe Clear Institute
Torrance, California, 90503
Ryan Dudley, 323-725-0657, rdudley@nicresearch.com
Steven Davis, MD
- Recruiting
Centers for Advanced ENT Care
Towson, Maryland, 21204
Holly Stadden, 410-821-5151, hstadden@cadentcare.com
Douglas Reh, MD
- Recruiting
Vital Prospects Clinical Research Institute
Tulsa, Oklahoma, 74136
Riley Pritzlaff, 918-392-4550, riley.pritzlaff@aaicenter.net
Iftikhar Hussain, MD
About this study
Official title: A 12-Week Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 mcg of OPN-375 Twice a Day (BID) in Adolescent Subjects With Chronic Rhinosinusitis Without Nasal Polyps
This is a 12-Week randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating the efficacy and safety of intranasal administration of 186 µg of OPN-375 twice a day (BID) in adolescent subjects with chronic rhinosinusitis without nasal polyps. The total planned number of subjects is approximately 84 adolescents (12-17 years of age) who will be randomly assigned to receive 1 of 2 study treatments using a 1:1 ratio (OPN-375 186 µg:placebo). The study includes a PK sub-study, in which up 14 subjects will be enrolled to obtain 10 completers.
Read the detailed description
The primary objective of this study is to compare the efficacy of intranasal administration of OPN-375 (fluticasone propionate)186 µg twice a day (BID) versus placebo in adolescents with chronic rhinosinusitis (CRS) without nasal polyps (sNP) using the endpoint of change from baseline in CRS symptoms as measured by a 7-day average instantaneous composite score of nasal symptoms (CSS) at the end of Week 4. The CSS is the sum of scores assigned to the symptoms congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior), on a scale of 0 (non-symptomatic) to 3 (severe symptoms). The total CSS can range from 0-9. Eligible study subjects will complete a 7 to 21 day screening period followed by a 12-week double-blind treatment period, for a total of approximately 15 weeks of participation. The study consists of 3 on-site study visits (screening/V1, randomization/V2, end of study/V3/Week 12) and two telephone calls at participation weeks 4 and 8.
The study will include a pharmacokinetic (PK) substudy in which PK assessment of 186 µg OPN-375 in up to 14 study subjects will be conducted in an open label fashion.
- Being tested
- OPN-375, Placebo
- Keywords
- Chronic Sinusitis, Chronic Rhinosinusitis, XHANCE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPN-375Drug
OPN-375 (fluticasone propionate) delivered via exhalation delivery system (EDS) BID
PlaceboDrug
Placebo solution administered via exhalation delivery system (EDS).
| Study group | Role | What they receive |
|---|---|---|
| Placebo BID | Placebo comparator | Double-Blind Treatment Phase: Intranasal administration of matching placebo BID x 12 weeks Receives: Drug: Placebo |
| OPN-375 186 µg BID | Active comparator | Double-Blind Treatment Phase: Intranasal administration of OPN-375 186 µg x 12 weeks Receives: Drug: OPN-375 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to the end of Week 4 in the average instantaneous CSS (evaluation of symptom severity immediately preceding the time of scoring).
The CSS consists of the sum of the scores (0-3) assigned to each of the following symptoms of CRS: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. The total CSS for each day can range from 0 to 9. Participants will report symptom severity immediately preceding the time of scoring every morning (AM). The baseline CSS is the average of the CSS's over the last 7 days of the single-blind run-in period. The end of Week 4 CSS is the average of the CSS's over the 7 days before Week 4.
Measured: 4 Weeks
Secondary outcomes (7)
Frequency of acute exacerbations of CRS over the 12-week treatment period
Acute exacerbations of CRS (AECRS) are defined as a worsening of symptoms that requires an escalation of treatment. The number of AECRS experienced by each participant will be recorded.
Measured: 12 weeks
Change from baseline to the end of Week 4 on CSS score in subjects using an intranasal steroid treatment for CRS within 30 days of Visit 1/Screening
The CSS consists of the sum of the scores (0-3) assigned to each of the following symptoms of CRS: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. The total CSS for each day can range from 0 to 9. Participants will report symptom severity immediately preceding the time of scoring every morning (AM). The baseline CSS is the average of the CSS's over the last 7 days of the single-blind run-in period. The end of Week 4 CSS is the average of the CSS's over the 7 days before Week 4. This outcome will assess this change in CSS specifically in the subgroup of participants who were symptomatic at trial entry despite reported use of an intranasal steroid for treatment of CRS within 30 days of Visit 1/Screening.
Measured: 4 Weeks
Change from baseline to the end of Weeks 8 and 12 in CSS
The CSS consists of the sum of the scores (0-3) assigned to each of the following symptoms of CRS: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. The total CSS for each day can range from 0 to 9. Participants will report symptom severity immediately preceding the time of scoring every morning (AM). The baseline CSS is the average of the CSS's over the last 7 days of the single-blind run-in period. The CSS for the end of Week 8 and Week 12 is the average of the CSS's over the 7 days before Week 8 and Week 12, respectively.
Measured: 8 Weeks; 12 Weeks
Change from baseline to the end of Weeks 4, 8 and 12 in four separate cardinal CRS symptoms
Participants will rate each of the following four cardinal symptoms of CRS every morning based on symptom severity immediately before reporting: nasal congestion, facial pain or pressure sensation, nasal discharge (anterior and/or posterior), and sense of smell. Participants will rate each symptom on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. Scores from the 7 days immediately preceding each timepoint will be averaged. The change in 7-day average score from baseline to Week 4, Week 8, and Week 12 for each symptom will be assessed individually.
Measured: 4 Weeks; 8 Weeks; 12 Weeks
Percent of subjects indicating improvement on the Patient Global Impression of Change (PGIC) at Week 12/ end of study.
The Patient Global Impression of Change (PGIC) survey consists of a single question asking participants to rate how much their symptoms have changed since beginning use of the study drug on a scale of 1 to 7, where 1 = Very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The percent of subjects indicating any improvement (minimal, much, or very much) will be assessed.
Measured: 12 Weeks
Change from baseline to Week 12 in the 5 domains of the SN-5 Questionnaire
The SN-5 questionnaire is a quality of life assessment that will be completed by the participant/parent. There are 5 specific symptom related questions (answered on a 7-point Likert scale on frequency of symptoms, where 1 = none of the time and 7 = all of the time), and 1 general quality of life question, answered on a visual analog scale from 0 (worst) to 10 (best). For this outcome, the change in score from baseline to Week 12/end of participation will be assessed for each of the 5 symptom related questions.
Measured: 12 Weeks
Change from baseline to Week 12 in overall quality of life as measured by the SN-5 Questionnaire
The SN-5 questionnaire is a quality of life assessment that will be completed by the participant/parent. There are 5 specific symptom related questions (answered on a 7-point Likert scale on frequency of symptoms, where 1 = none of the time and 7 = all of the time), and 1 general quality of life question, answered on a visual analog scale from 0 (worst) to 10 (best). This outcome will assess the change in score from baseline to Week 12/end of participation for general quality of life question.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2025
- Study start28 Jul 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Rhinosinusitis Without Nasal PolypsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Optinose US Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Paratek Pharmaceuticals Inc
- Responsible party
- Sponsor
- Investigators
- Amy Manley, Study chair, Paratek Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06850805
- Sponsor's protocol ID
- OPN-FLU-CS-3207
- Acronym
- Re-Open 3
- Status last verified
- Sep 2026
- First submitted
- 14 Feb 2025
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No