Clinical trial NCT03747458: OPN-375 Efficacy and Safety in Adolescents With Bilateral Nasal Polyps
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bilateral Nasal Polyposis
Lead sponsor: Optinose US Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-20
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. or agree to abstinence.
3. Ability to read and speak English
4. 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)
5. 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)
6. 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.)
7. 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)
8. 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)
9. 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.
10. 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.
11. Must demonstrate correct use of the demo exhalation delivery system (EDS).
12. 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 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) Visit 1 (Screening)
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 to diagnose or grade polyps if the subject requires nasoendoscopy
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 an allergy or hypersensitivity to any excipients in 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. 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)
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 glaucoma or ocular hypertension (intraocular pressure \>21 mmHg)
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) clinically significant history of drug or alcohol use, abuse, or dependence)
28. Positive urine drug screen at Visit 1 (Screening) 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

Primary outcomes:
measure: Change in nasal congestion/obstruction symptoms (mild, moderate, severe) at the end of Week 4
timeFrame: 4 Weeks
measure: Mean change from baseline at Week 16 in total polyp grade
timeFrame: 16 Weeks
Secondary outcomes:
measure: Change in bilateral polyp grade over time
timeFrame: 16 Weeks
measure: Percentage of subjects with a ≥1 point improvement in polyp grade
timeFrame: 16 Weeks
measure: Percentage of subject with a grade of 0 on at least one side of the nose
timeFrame: 16 Weeks
measure: 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)
timeFrame: 16 Weeks
measure: 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)
timeFrame: 16 Weeks
measure: 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)
timeFrame: 16 Weeks
measure: 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)
timeFrame: 16 Weeks
measure: 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
timeFrame: 16 Weeks
measure: Subjects will assess their global impression of change since starting the study drug using the PGIC scale
timeFrame: 16 Weeks
measure: Subjects will assess their change in quality of life since starting the study drug using the quality of life questionnaire (SN-5).
timeFrame: 16 Weeks
measure: Proportion of subjects eligible for surgical intervention (independent of actual surgery performed)
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
Other outcomes:
measure: Assessment of safety from physical examination-measuring weight
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
measure: Assessment of safety from physical examination-measuring height
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
measure: Assessment of safety by recording the severity of AEs
timeFrame: 16 Weeks
measure: Assessment of safety by nasal examination
timeFrame: 16 Weeks
measure: Assessment of safety by ocular examination-visual acuity
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
measure: Assessment of safety by ocular examination-Intraocular Pressure
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
measure: Assessment of safety by ocular examination-Cataract Evaluation
timeFrame: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
measure: Assessment of safety measuring vital signs (blood pressure)
timeFrame: 16 Weeks
measure: Assessment of safety measuring vital signs (pulse)
timeFrame: 16 Weeks
measure: Assessment for safety from the collection of information for concomitant medications usage
timeFrame: 16 Weeks
measure: Assessment of pharmacokinetics - AUC(0-t) (pg*hr/mL)
timeFrame: 8 hours, 1 to 2 weeks before randomization
measure: Assessment of pharmacokinetics - AUC(0-∞) (pg*hr/mL)
timeFrame: 8 hours, 1 to 2 weeks before randomization
measure: Assessment of pharmacokinetics - AUCex (%)
timeFrame: 8 hours, 1 to 2 weeks before randomization
measure: Assessment of pharmacokinetics - Cmax (pg/mL)
timeFrame: 8 hours, 1 to 2 weeks before randomization
measure: Assessment of pharmacokinetics - tmax (h)
timeFrame: 8 hours, 1 to 2 weeks before randomization
measure: Assessment of pharmacokinetics - t1/2 (h)
timeFrame: 8 hours, 1 to 2 weeks before randomization
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Gilbert
country: United States
facility: Arizona Allergy and Immunology Research
state: Arizona
city: Gilbert
country: United States
facility: San Tan Allergy & Asthma
state: Arizona
city: Bakersfield
country: United States
facility: Kern Research
state: California
city: Fresno
country: United States
facility: Central California Clinical Research
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Redwood City
country: United States
facility: Allergy and Asthma Consultants
state: California
city: Roseville
country: United States
facility: Sacramento ENT
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine, Section of Otolaryngology
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Children's Specialty Care
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center - Department of Otorhinolaryngology
state: Illinois
city: Chicago
country: United States
facility: Chicago ENT
state: Illinois
city: Louisville
country: United States
facility: Kentuckiana ENT
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center, Otorhinolaryngology Department
state: Louisiana
city: Minneapolis
country: United States
facility: Children's Minnesota
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Medical Center
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Allergy Asthma & Immunology Research Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: Allergy, Asthma & Clinical Research Center
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C.
state: Oklahoma
city: Charleston
country: United States
facility: MUSC Department of Otolaryngology, Head and Neck Surgery
state: South Carolina
city: Orangeburg
country: United States
facility: Carolina ENT
state: South Carolina
city: San Antonio
country: United States
facility: STAAMP Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical School - Otolaryngology
state: Virginia
city: Spokane Valley
country: United States
facility: Spokane ENT
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Optinose US Inc.
name: Kim Koob
role: STUDY_DIRECTOR
affiliation: Optinose US Inc.
name: John Messina
role: STUDY_CHAIR
References: