OPN-FLU-CS-3206

• Research type

  Research Study

• Full title

  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 Sinusitis Without the Presence of Nasal Polyps.

• IRAS ID

  266771

• Contact name

  Carl Philpott

• Contact email

  C.Philpott@uea.ac.uk

• Sponsor organisation

  OptiNose US, Inc.

• Eudract number

  2019-000648-86

• Clinicaltrials.gov Identifier

  NCT03960580

• Duration of Study in the UK

  1 years, 4 months, 23 days

• Research summary

  Summary of Research
  OptiNose has developed OPN-375 (proprietary name XHANCE®) as an intranasal drug delivery system with the intention to improve the performance of fluticasone propionate in the treatment of nasal inflammatory diseases by facilitating deposition of the topical steroid in regions affected by local inflammation. Delivery of drug using an Exhalation Delivery System (EDS) is intended to improve reproducibility of nasal delivery, particularly deposition of the topical steroid to the middle meatus where the sinuses ventilate and drain (ostiomeatal complex). OPN-375 is also intended to address user preference associated with reduced drip-out (posterior and anterior) and taste, and to improve tolerability and efficiency by significantly reducing loss of drug to nontarget sites such as the gastrointestinal (GI) tract and lungs.
  Fluticasone propionate is an androstane glucocorticoid with high lipophilicity, high selectivity and affinity for the glucocorticoid receptor, low oral and nasal systemic absorption, and rapid metabolic clearance. It is approved in many countries for use in the treatment of dermatosis (topical), rhinitis (intranasal), and asthma and chronic obstructive pulmonary disease (COPD) (inhaled) and is one of the most well studied and characterized glucocorticoids in clinical use today.

  Summary of Results
  This was 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. The primary objective of this study was 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:

  A change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.
  A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses. Of the 223 subjects who were randomized (ITT Analysis Set), 222 (99.6%) received at least 1 dose of study drug (SAS), 220 (98.7%) were in the FAS, and 210 (94.2%) completed 24 weeks of double-blind study treatment. A total of 12 (5.4%) subjects discontinued randomized study treatment: 6 (8.0%) placebo recipients and 6 (4.1%) OPN-375 recipients (3 [4.1%] subjects in the 186 µg group and 3 [4.1%] subjects in the 372 µg group). The most common reasons given for discontinuation of OPN-375 (both dose levels combined) and placebo were AEs, lack of efficacy (LOE), and withdrawal by subject. The mean age of the 222 treated subjects was 48.4 years (mean ages across the 3 study groups were similar and ranged from 47.1 to 49.4 years). Overall, 111 (50%) subjects were male and 111 (50%) were female. The population was predominantly White (98.6%). There was a similar distribution of age, gender, race, and ethnicity among subjects in each treatment group. The 3 treatment groups were similar with respect to the proportion of subjects who had a previous sinus surgery for which randomization was stratified. Overall, 57 (25.7%) subjects reported using a standard nasal steroid spray for chronic sinusitis at trial entry.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  19/SC/0348

• Date of REC Opinion

  1 Oct 2019

• REC opinion

  Further Information Favourable Opinion