OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps

16-Week Randomized Double-Blind Placebo Controlled Parallel-Group Multicenter Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day in Adolescents With Bilateral Nasal Polyps Followed With 12-Week Open-Label Treatment Phase

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 72 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.

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.

Inclusion Criteria:

1. Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).

2. Female subjects, if sexually active, must,

   1. 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
   2. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
   3. be abstinent.

3. 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 (hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline).

4. 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).

5. 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 a 7 day period during the single-blind run-in period. (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)

6. 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 2015 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study (GINA 2015). Subjects receiving inhaled fluticasone alone or in combination may not participate in the PK sub-study.

7. 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, inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). [Note: intranasal antibiotics and saline are permissible]

8. 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 Visit 3 (Week 4) of the study.

9. Subjects (with assistance from parent or legal guardian if needed) must demonstrate the ability to complete the daily diary during the run-in period to be eligible for randomization.

10. Must demonstrate correct use of the demo EDS.

11. 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.

Exclusion Criteria:

1. Pregnancy or lactation
2. Has a history of cystic fibrosis
3. Have used XHANCE (fluticasone propionate) nasal spray within the past 2 months
4. Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
5. Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
6. Have known history of nasal septum erosion, ulceration or perforation, or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
7. Other significant nasal pathology or abnormal anatomy
8. Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
9. History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime)
10. Have had any surgery on the nasal septum
11. History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
12. History of any surgical procedure that prevents the ability to accurately diagnose or grade polyps
13. Current, ongoing rhinitis medicamentosa (rebound rhinitis)
14. Have significant oral structural abnormalities (e.g., a cleft palate)
15. History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
16. 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.
17. Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
18. Have a hypersensitivity to any excipients in the study drug
19. 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
20. Have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1
21. Have nasal or oral candidiasis
22. Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
23. 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
24. History or current diagnosis of any form of glaucoma or ocular hypertension (i.e., >21 mm Hg)
25. History of intraocular pressure elevation on any form of steroid therapy
26. 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
27. A recent (within 1 year of Visit 1 [Screening]) history of drug or alcohol abuse or dependence
28. Positive urine drug screen at screening visit for stimulants, opioids, or cocaine
29. Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
30. 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.