Evaluation of Nitric Oxide Nasal Spray (NONS) for Treatment of Recurrent Acute Rhinosinusitis

Recurrent Acute Rhinosinusitis Clinical Trial

— NONS-RARS-01  

Official title:

Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2 Clinical Efficacy Study Evaluating Nitric Oxide Nasal Spray (NONS) Compared to Saline Nasal Spray as an Early Treatment for Recurrent Acute Rhinosinusitis (RARS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06264141
• Other study ID #: NONS-RARS-01
• Status: Recruiting
• Phase: Phase 2
• Start date: January 16, 2024
• Est. completion date: September 2024

Study information

• Verified date: February 2024
• Source: Sanotize Research and Development corp.
• Contact: Chris Miller, PhD
• Phone: 1-855-357-7398
• Email: chris[@]sanotize.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A two-week therapy of nitric oxide nasal spray (NONS) vs Placebo (saline nasal spray) initiated immediately after the onset of a new Recurrent Acute Rhinosinusitis (RARS) episode to assess the acceleration to clinical success (cured/much improved symptoms), lack of use of intranasal corticosteroids (INCS) (Day 5, or thereafter) and rescue oral antibiotics (ATBs) (Day 8, or thereafter) after initiation of nitric oxide releasing solution (NORS) platform therapy.

Description:

Study Design:

This is a multicenter, randomized, double-blind placebo-controlled, two-arm, parallel-group, phase 2 clinical trial to determine the efficacy and safety of NONS to treat recurrent acute (bacterial) rhinosinusitis (RARS).

Nitric oxide-releasing solution (NORS) therapy administered as NONS, has the potential to shorten RARS episodes and may reduce the concomitant use of INCS, oral non-steroidal anti-inflammatory drugs (NSAIDS) and oral ATBs used to manage this condition. Suitable candidates will be randomized to a 2-week course of nitric oxide nasal spray (NONS) compared to saline nasal spray (1:1 ratio, administered as five doses daily). RARS symptoms efficacy response will be measured twice daily, after initiation of study medication (Day 1 to Day 15), then once daily to the end of the study (Day 16 to Day 29). The goal of NONS therapy is to accelerate the time to achieve RARS symptoms resolution, defined as a clinical success (cured or much improved sinusitis symptoms; primary endpoint assessment at Day 8), minimize the use of INCS and the avoidance of rescue oral ATBs (both secondary endpoints) over the study period (Day 1 to Day 29). Participants will be enrolled between RARS episodes while asymptomatic, and on study for up to 4 months or until their next recurrence of RARS at which time study procedures and medication begin.

Adults (18 years or older) presenting with a history of mild to severe RARS symptoms (nasal obstruction (congestion), purulent nasal discharge, postnasal drip, headache, facial pain), signs (such as facial swelling), and other nonspecific signs/symptoms of fever and malaise are eligible.

The primary endpoint is is the time to sinus symptoms resolution, i.e., being cured or much improved (participant reported clinical success) after 7 days of therapy,

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: September 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. At least aged 18 years old at the time of consent (19 years depending on the age of majority in the Canadian province/territory).

2. History of recurrent acute bacterial sinusitis (ABS) with at least three episodes in the previous 12 months with at least two episodes requiring ATB therapy (with symptom-free periods between infections).

3. History of at least two moderately severe symptoms of acute rhinosinusitis (anterior (nasal) and posterior (postnasal drip) secretions, nasal obstruction (congestion), headache or facial pain/pressure during a typical RARS episode.

4. If female, be surgically sterile or post-menopausal (no menses for at least 12 months), or if of childbearing potential, must be using an acceptable method of contraception such as a combination estrogen/progestin hormonal contraceptive (oral or injected) for at least 1 month prior to Screening, or such items as an intrauterine device (IUD), intrauterine system (IUS), transdermal hormonal implant, vaginal hormonal ring, or 2 forms of the following: diaphragm, cervical cap, patch, condom, spermicide, or sponge. Total abstinence is permitted. Must agree to agree continue using contraception for the duration of the study medication treatment.

5. If male, be surgically sterile, or agree to use appropriate contraception (latex condom with spermicide) when engaging in sexual activity and agree to not donate sperm for the duration of the study medication treatment.

6. Be reasonable stable health (i.e., diagnosed chronic illnesses that are not deemed stable by the participant's primary care physician), or in the opinion of the Investigator, based on medical history (i.e., absence of any clinically relevant abnormality) during Screening.

7. Be able to understand and provide written, informed consent.

8. Must be able to attend on-site and virtual study visits.

Exclusion Criteria:

1. Complicated RARS (orbital or intracranial involvement).

2. Symptoms attributed to sinus disease for longer than 4 weeks.

3. RARS with multiple courses of antimicrobial therapy failures (in previous 2 years, 3 or more episodes treated with 2 or more ATBs).

4. Disease history consistent with severe allergic or seasonal rhinitis (requiring oral cortico-steroids to manage intractable nasal symptoms).

5. Isolated frontal and sphenoidal clinical disease (given the different pathophysiology and etiologic pathogens).

6. History of nasal polyposis.

7. History of abnormal sinus pathology.

8. Previous sinus surgery.

9. Participants with cystic fibrosis.

10. Recurrent moderate epistaxis.

11. Participants with chronic obstructive pulmonary disease (COPD).

12. Participants with severe asthma (per European Respiratory Society (ERS)/American Thoracic Society (ATS) 2014).

13. Immunocompromised participants or participants with other medical conditions that may affect interpretation of the effect of trial drugs.

14. Allergic to any of the trial drugs.

15. Females who are breastfeeding, pregnant, or attempting to become pregnant.

16. Participants who have conditions that participation is not in their best interest.

17. Participants whose participation in the study, in the opinion of the Investigator, have a condition which would interfere with their ability to adhere to the protocol (e.g., participants whom are mentally or neurologically disabled and whom are considered not fit to their participation in the study), interfere with the assessment of the investigational product, or compromise the safety of the participant or the quality of the data.

18. Participants who are unable to sign the informed consent.

Related Conditions & MeSH terms

• Recurrence
• Recurrent Acute Rhinosinusitis
• Sinusitis

Intervention

Drug:
• Nitric Oxide Releasing Solution
The Sponsor designed a dual chamber nasal spray bottle for NORS administration. Components are mixed from two chambers to create the final NO-producing formulation. The liquid contains NO at 0.11 ppm*hour, which acts as a viricidal agent. Instructions for storing, preparing, and administering the study treatment will be provided to participants.

Device:
• Nasal spray with isotonic saline
The Sponsor designed a dual-chamber nasal spray bottle for NORS administration. The bottle will be filled with normal saline before being provided to the participant.

Locations

Country	Name	City	State
Canada	Intermed Groupe Santé	Chicoutimi	Quebec
Canada	Okanegan Clinical Trials	Kelowna	British Columbia
Canada	Cliantha Research	Mississauga	Ontario
Canada	Alpha Recherche Clinique LeBourneuf	Québec City	Quebec
Canada	Alpha Recherche Clinique Val-Belair	Québec City	Quebec
Canada	Richmond Clinical Trials (Okanagan Clinical Trials Satelite Site)	Richmond	British Columbia
Canada	Clinical Research of Ontario	Scarborough	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sanotize Research and Development corp.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of ATB courses required as a rescue treatment	To record the number of antibiotic courses taken by individual participants.	29 days
Other	Time (days) to the initiation of NSAIDs	To record the duration to study participants receiving NSAIDs.	29 days
Other	Proportion of participants requiring NSAIDs	To record the fraction of participants requiring NSAIDs.	29 days
Other	Time (days) to each symptom being cured or much improved	To record the duration to symptom cure/improvement by symptom.	29 days
Other	Proportion of participants being cured or much improved for each symptom	To record the fraction of participants with symptom improvement per each symptom.	Day 8, 15 & 29
Other	Proportion of participants achieving at least a 50% reduction in sinusitis symptoms (by MRSS)	To record the fraction of participants reporting significant improvement on their major rhinosinusitis symptom score.; MRSS minimum score value is 0 (no symptoms), maximum score value is 15 (worst symptoms).	Day 5, 8, 15 & 29
Primary	Primary endpoint is the time to sinus symptoms resolution	To demonstrate superior efficacy of NONS compared to saline nasal spray in the early treatment of RARS. The primary objective is to demonstrate that NONS accelerates the time to achieve clinical success as determined by a higher percentage of participants having resolved or much improved sinusitis symptoms after 7 days of therapy.	8 days
Secondary	Time (days) to full recovery from sinusitis (participant reported)	To record the rate of recovery for study participants.	29 days
Secondary	Time (days) to sinus symptoms resolution, i.e., being cured or much improved (participant reported clinical success)	To record the improvement of symptoms among study participants.	29 days
Secondary	Time (days) to the initiation of rescue oral ATB(s), i.e., treatment failure i.e., treatment failure	To record the frequency of study participants receiving rescue antibiotics.	29 days
Secondary	Time (days) to initiation of INCS	To record the rate of study participants starting corticosteroids.	29 days
Secondary	Proportion of participants requiring INCS	To record the fraction of study participants requiring corticosteroids.	Day 5, 8, 15 & 29
Secondary	Proportion of participants requiring rescue oral ATBs	To record the fraction of study participants requiring antibiotics.	Day 5, 8, 15 & 29
Secondary	Proportion of participants recovered from sinusitis	To record the fraction of study participants who recover	Day 5, 8, 15 & 29
Secondary	Proportion of participants with rapidly worsening symptoms requiring the use of INCS and oral ATBs	To record the fraction of study participants whose symptoms required corticosteroids and antibiotics.	29 days
Secondary	Proportion of participants achieving at least a 9-point improvement change from baseline in Sinonasal Outcome Test (SNOT)-22	To record the fraction of study participants who show improvement in survey scores.	Day 8 & 15
Secondary	Tolerability and safety of NONS	Number of participants with clinically significant changes from baseline in Adverse events	29 days
Secondary	Proportion of participants with clinically significant changes from baseline in vital signs	Vital sign measurements includes systolic/diastolic blood pressures, pulse rate, respiratory rate and body temperature	29 days
Secondary	Proportion of participants with clinically significant changes from baseline in laboratory parameters	Laboratory investigation includes hematology and chemistry panels	29 days
Secondary	Number of participants with clinically significant changes from Baseline in physical examinations		29 days