Nitric Oxide Releasing Sinus Irrigation (NOSi) to Treat Recalcitrant Chronic Rhinosinusitis (RCRS)

Phase 2 Trial to Evaluate Safety & Efficacy of Topical Nitric Oxide Releasing Sinus Irrigation (NOSi) as Compared to Budesonide-Saline (Control) in the Management of Biofilm-Associated Recalcitrant Chronic Rhinosinusitis (RCRS)

This a single center, randomized controlled trial to evaluate safety & efficacy of topical nitric oxide releasing sinus irrigation (NOSi) as compared to budesonide-Saline (Control) in the management of biofilm-associated recalcitrant chronic rhinosinusitis (RCRS). It is hypothesized that a daily treatment of NOSi over a 6-week period will be safe and effective at reducing clinical symptoms associated with RCRS.

This is a prospective, single center, Phase 2, double-blinded, randomized, controlled, parallel group trial study. Up to fifty-four (54) participants will be enrolled (based on power analysis based on outcomes from a previous dose-tolerance study. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria and none of the exclusion criteria will be entered into the study and randomized in to the Investigational Medicinal Product (IMP) or Non Investigational Medicinal Product (NIMP) at a 2:1 ratio (NOSi:Budesonide). Each participant will be managed as an outpatient for the 42 days of the study. Participants will be administered NOSi or budesonide in saline by self-administration, at home, as a sinus irrigation to their nasopharynx and sinuses once a day. Participants will be asked to return to the clinic for evaluations on Day 21(±2), Day 43(±2) and Day 63 (±2) following the start of study interventions.

Inclusion Criteria:

1. Written informed consent must be obtained from the participant prior to entering the study.
2. Must be ≥ 19 years of age unless local laws dictate otherwise
3. English speaking
4. Willing and able to return to the study site for protocol required visits.
5. Documented diagnosis of chronic sinusitis with biofilm after a treatment of at least 3 months of a combination of well executed sinus surgery, regular irrigation with topical steroids or a mucosal atomization device and surfactants and at least one course of culture directed oral antibiotics
6. Persistent or worsening symptoms within 30 days of wash-in with budesonide. Specifically, documented by two SNOT-22 scores greater than or equal to 20 indicating stable (within 9 points) or worsening symptoms. SNOT-22 evaluations must be at least 7 days and no more than 30 days apart. Second SNOT-22 must be used as baseline.
7. Participant has been on a stable course of only Pulmicort and saline irrigation for a minimum of 30 days prior to randomization
8. Must be willing to use an adequate and documented form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP

Exclusion Criteria:

1. Presence of prior history of sinonasal tumors
2. Isolated sphenoid sinusitis or other sinus cavities that are not accessible to a nasal/sinus rinse as done by the patient in the head forward position
3. Autoimmune diseases affecting the upper airway eg Systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis etc
4. Immuno-compromised patients, and patients with impairment in mucociliary function (e.g., cystic fibrosis, Kartagener syndrome)
5. Severe underlying disease with anticipated survival less than 6 months
6. Females who are pregnant, breastfeeding, or plan to become pregnant during the course of the study up to 1 weeks after the last dose/study visit
7. Has used any investigational drug(s) within 30 days preceding randomization visit (Day 1);
8. Suffers from a condition, which, in the opinion of the medical investigator, would compromise their safety and / or their adherence to the study protocol
9. Systemic antibiotics, corticosteroids or antifungals within 30 days of randomization
10. Intranasal or irrigation with antibiotics, antifungals or antiseptics or any other sinusitis treatment other than Pulmicort within 30 days of randomization
11. Has a family member living in the same household, also enrolled or planning to enroll in this study.