OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps
- Conditions
- Bilateral Nasal Polyposis
- Interventions
- Drug: OPN-375
- Registration Number
- NCT03747458
- Lead Sponsor
- Optinose US Inc.
- Brief Summary
This is a 16-Week Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day (BID) in Adolescents with Bilateral Nasal Polyps followed by a 12-Week Open-Label Treatment Phase. The total planned number of subjects is approximately 120 adolescents (12-17 years of age) who will be randomly assigned to receive 1 of 2 study treatments using a 2:1 ratio (OPN-375 186 μg: Placebo). For the PK sub-study, up to 14 subjects will be enrolled to obtain 10 completers.
- Detailed Description
The primary objective of this study is to evaluate the efficacy of intranasal administration of OPN-375 186 μg Twice a Day (BID) versus placebo in adolescents with bilateral nasal polyposis and nasal congestion by analyzing the reduction of nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning diary symptom scores and the reduction in total polyp grade at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
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Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).
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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
- or agree to abstinence.
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Ability to read and speak English
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All female subjects not documented to be infertile (e.g., infertility due to congenital abnormality or surgical sterilization) must have a negative serum or urine beta-human chorionic gonadotropin (β-hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline)
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Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening)
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Must report at least mild symptoms of nasal congestion/obstruction as demonstrated by an average morning nasal congestion/obstruction score of at least 1.0 over the last 7 days of the run-in period (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)
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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 2005 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study. Visit 1 (Screening)
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Must be able to cease treatment with intranasal medications including, but not limited to, intranasal oxymetazoline or any other decongestants, intranasal antihistamines, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, as well as inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). (Note: intranasal antibiotics and saline are permissible)
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If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to the Visit 1 (Screening), and agree to not change the dose of these medications until after Visit 3 (Week 4) of the study.
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Subject (with assistance from parent or legal guardian if needed) must demonstrate the ability to correctly complete the daily diary during the run-in period to be eligible for randomization.
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Must demonstrate correct use of the demo exhalation delivery system (EDS).
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Must be capable, in the opinion of the investigator, of providing assent and the appropriate parent(s) or guardian must provide an informed consent to participate in the study.
- Pregnancy or lactation
- Has a history of cystic fibrosis
- Have used XHANCE® (fluticasone propionate) nasal spray within the past 2 months
- Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
- Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
- Have history of nasal septum erosion, ulceration or perforation or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
- Other significant nasal pathology or abnormal anatomy
- Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
- History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime) Visit 1 (Screening)
- Have had any surgery on the nasal septum
- History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
- History of any surgical procedure that prevents the ability to accurately to diagnose or grade polyps if the subject requires nasoendoscopy
- Current, ongoing rhinitis medicamentosa (rebound rhinitis)
- Have significant oral structural abnormalities (e.g., a cleft palate)
- History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
- Purulent nasal infection (recent fever or symptoms of lethargy), acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with one of these infections may be rescreened after 4 weeks
- Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
- Have an allergy or hypersensitivity to any excipients in study drug
- Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral or parenteral steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma
- Currently receiving Nucala (mepolizumab), Cinquair (reslizumab), Dupixent (dupilumab), or Omalizumab (Xolair®) (note patients should not be removed from their therapy for the sole purpose of study participation)
- Have nasal or oral candidiasis
- Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
- Any serious or unstable concurrent disease, psychiatric disorder, or any significant concomitant medical 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, or pose a specific risk to the subject due to study participation
- History or current diagnosis of glaucoma or ocular hypertension (intraocular pressure >21 mmHg)
- History of intraocular pressure elevation on any form of steroid therapy
- Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet OR, less than a Grade 1 cataract with associated visual impairment
- A recent (within 1 year of Visit 1 (Screening) clinically significant history of drug or alcohol use, abuse, or dependence)
- Positive urine drug screen at Visit 1 (Screening) for stimulants, opioids, or cocaine
- Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
- Parents, guardian or caregivers of the subject who are employees 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, as well as family members of the employees or the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OPN-375 186 μg BID OPN-375 Double-Blind Treatment Phase: OPN-375 186 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 186 μg BID x 12 weeks Placebo OPN-375 Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks
- Primary Outcome Measures
Name Time Method Mean change from baseline at Week 16 in total polyp grade 16 Weeks Change in total polyp grade (sum of scores from both nasal cavities) at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Change in nasal congestion/obstruction symptoms (mild, moderate, severe) at the end of Week 4 4 Weeks Change in nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning (AM) diary symptom scores (ADS7-IA). The nasal symptom scale is what is used to score the nasal congestion/obstruction score, which is recorded in the diary. Nasal symptom scale is graded on a scale of 0=no symptom, 1=mild symptom, 2=moderate symptom, 3=severe symptom.
- Secondary Outcome Measures
Name Time Method Percentage of subjects with a ≥1 point improvement in polyp grade 16 Weeks nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Percentage of subject with a grade of 0 on at least one side of the nose 16 Weeks nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Change in diary symptom scores for the sense of smell, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores) 16 Weeks Sense of smell will be scored on a scale from 0 (normal) to 3 (absent, no sense of smell)
Subjects will assess their global impression of change since starting the study drug using the PGIC scale 16 Weeks Subject global impression of change will be assessed using a subject-completed PGIC scale, with a single question rated from 1=very much improved to 7=very much worse
Subjects will assess their change in quality of life since starting the study drug using the quality of life questionnaire (SN-5). 16 Weeks Quality of life assessment using the SN-5 Questionnaire, a subject/parent-completed questionnaire that consists of 5 specific symptoms-related questions (answered on a 7-point Likert scale on the frequency of symptoms, 1=none of the time, 7=all of the time), and 1 general overall quality of life question (answered on a visual analog scale from 0 to 10, worst to best).
Change in bilateral polyp grade over time 16 Weeks nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril
Change in diary symptom scores for the symptoms of rhinorrhea, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores) 16 Weeks The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Change in diary symptom scores for the symptoms of facial pain or pressure, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores) 16 Weeks The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Change in diary symptom scores for the symptoms of nasal congestion/obstruction, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores) 16 Weeks The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
The proportions of subjects who have reductions in the AM and PM, instantaneous and reflective, average nasal congestion/obstruction symptom scores by 0.5 or more points from baseline to the end of the double-blind treatment phase 16 Weeks The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom)
Proportion of subjects eligible for surgical intervention (independent of actual surgery performed) Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination) The assessment criteria are as follows:
* Subject has had moderate symptoms of congestion from nasal polyposis for at least 3 months.
* Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for at least 6 weeks.
* Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for at least 6 weeks.
* Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score \> 2 in at least 1 nostril). Also assess each subject's eligibility for surgery based on specific of criteria (see Section 12) independent of whether the subject actually undergoes surgery.
Trial Locations
- Locations (29)
Arizona Allergy and Immunology Research
🇺🇸Gilbert, Arizona, United States
Children's Minnesota
🇺🇸Minneapolis, Minnesota, United States
Eastern Virginia Medical School - Otolaryngology
🇺🇸Norfolk, Virginia, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
San Tan Allergy & Asthma
🇺🇸Gilbert, Arizona, United States
Carolina ENT
🇺🇸Orangeburg, South Carolina, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Spokane ENT
🇺🇸Spokane Valley, Washington, United States
University of Rochester
🇺🇸Rochester, New York, United States
STAAMP Research
🇺🇸San Antonio, Texas, United States
Allergy Asthma & Immunology Research Institute
🇺🇸Charlotte, North Carolina, United States
University of Missouri Medical Center
🇺🇸Columbia, Missouri, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Vital Prospects Clinical Research Institute, P.C.
🇺🇸Tulsa, Oklahoma, United States
Sacramento ENT
🇺🇸Roseville, California, United States
Kern Research
🇺🇸Bakersfield, California, United States
Central California Clinical Research
🇺🇸Fresno, California, United States
Allergy and Asthma Consultants
🇺🇸Redwood City, California, United States
Rush University Medical Center - Department of Otorhinolaryngology
🇺🇸Chicago, Illinois, United States
Chicago ENT
🇺🇸Chicago, Illinois, United States
Clinical Research Center of Alabama
🇺🇸Birmingham, Alabama, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Yale School of Medicine, Section of Otolaryngology
🇺🇸New Haven, Connecticut, United States
Kentuckiana ENT
🇺🇸Louisville, Kentucky, United States
Allergy, Asthma & Clinical Research Center
🇺🇸Oklahoma City, Oklahoma, United States
MUSC Department of Otolaryngology, Head and Neck Surgery
🇺🇸Charleston, South Carolina, United States
Ochsner Medical Center, Otorhinolaryngology Department
🇺🇸New Orleans, Louisiana, United States
Nemours Children's Specialty Care
🇺🇸Jacksonville, Florida, United States