A 24-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps
Overview
- Phase
- Phase 3
- Intervention
- OPN-375
- Conditions
- Chronic Rhinosinusitis
- Sponsor
- Optinose US Inc.
- Enrollment
- 223
- Locations
- 87
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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
Detailed Description
The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints: 1. A change from baseline in symptoms as measured by the average morning composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4. 2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
OPN-375 186 μg BID
OPN-375 186 μg BID x 24 Weeks
Intervention: OPN-375
OPN-375 372 μg BID
OPN-375 372 μg BID x 24 Weeks
Intervention: OPN-375
Placebo
Matching Placebo BID x 24 Weeks
Intervention: OPN-375
Outcomes
Primary Outcomes
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
Time Frame: 4 Weeks
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.
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses.
Time Frame: Baseline, Week 24
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%.
Secondary Outcomes
- 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)
- Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score(Baseline, Week 24)
- Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment.(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment.(24 weeks)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment.(24 weeks)
- Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined(24 Weeks)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined(24 weeks)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations(24 Weeks)
- Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)(12 Weeks, 24 Weeks)
- Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)(Week 4, Week 24)
- Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)(24 Weeks)
- Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS).(24 Weeks)
- Change in the SF-36v2 Physical Component Score (PCS)(24 Weeks)
- Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)(24 Weeks)
- Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)(24 Weeks)
- Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™(24 Weeks)
- Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument(24 Weeks)
- Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument(24 Weeks)
- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24(Baseline, Week 24)
- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.(Baseline, Week 24)
- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery(Week 24)