Barrier-forming, drug-free nasal spray reduces allergic symptoms induced by house dust mite allergen.

BACKGROUND: House Dust Mite (HDM) is the most common indoor allergen triggering allergic symptoms. First-line pharmacotherapy treatment is recommended in international guidelines, while the avoidance of allergens represents a still unmet guideline principle. AM-301 is a new non-pharmacological nasal spray that creates a protective gel-like barrier on the nasal mucosa, preventing the contact with the allergens. METHODS: This randomized, open-label, 3-period crossover study assessed the efficacy and safety of AM-301. The objective was to determine whether AM-301 reduces allergic rhinitis (AR) symptoms in patients exposed to HDM allergens. Adults with confirmed Perennial Allergic Rhinitis (PAR; n = 37) were exposed to HDM allergen in a controlled Allergen Exposure Chamber before and during a treatment course of AM-301 (in six different sequences) within 3 weeks (A: One spray AM-301 per nostril/B: Two sprays AM-301 per nostril/C: no treatment). For the primary efficacy analysis, data from the total nasal symptom score (TNSS) were pooled from treatment A + B (D) and analyzed with Analysis of Covariance Model. As secondary endpoints, single time points, visits and symptoms were analyzed. RESULTS: The primary endpoint (overall change in TNSS from baseline over all three visits) showed significant results (p = 0.0085). A comparable alleviation of all four symptoms (itchy nose, nasal congestion, runny nose, sneezing) by the protective layer started to emerge after 40 min and lasted up to 180 min (end of challenge). AM-301 resulted to be safe and well-tolerated. CONCLUSION: AM-301 significantly reduced HDM-related allergic symptoms in a standardized allergen challenge. Protection was observed to last up to 180 min.

Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray - AM-301.

OBJECTIVE: The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability. SIGNIFICANCE: The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects. AM-301 has shown promising efficacy and safety in the nasal epithelium against viruses (in vitro) and pollen (clinical). METHODS: Technical part (i) spray characterization was performed with a validated droplet size distribution method; evaluation of the rheological properties of the formulation was performed by a validated amplitude sweep method and a validated oscillation, rotation, oscillation; Clinical part (ii) nasal and oropharyngeal endoscopy were used to provide a semi-quantitative evaluation of distribution and residence time of fluorescein-labelled AM-301 in the nose and oropharynx of healthy volunteers; (iii) tolerability and safety. RESULTS: (i) The non-Newtonian rheological properties of the formulation allow AM-301 to be sprayed and then to revert to a gel to prevent run-off from the nasal cavity; (ii) the formulation remains on the inferior turbinate, septum and oropharynx of volunteers for up to 210 min and on the middle turbinate for up to 60 min; two nasal sprays provide no substantial benefit over a single application with regards to coverage or retention; (iii) the spray is well tolerated. CONCLUSIONS: Single dose spray delivery of AM-301 provides extended coverage of the nasal mucosa up to the inferior turbinates.

Efficacy and Safety of a Drug-Free, Barrier-Forming Nasal Spray for Allergic Rhinitis: Randomized, Open-Label, Crossover Noninferiority Trial.

INTRODUCTION: Symptoms of allergic rhinitis can be reduced by nonpharmacological nasal sprays that create a barrier between allergens and the nasal mucosa. A new nasal spray (AM-301) containing the clay mineral bentonite was tested for its ability to reduce symptoms of grass pollen. METHODS: This open-label, crossover, noninferiority trial compared the efficacy and safety of AM-301 to that of hydroxypropyl methylcellulose (HPMC; Nasaleze® Allergy Blocker), an established barrier method. Adults with seasonal allergic rhinitis were exposed to Dactylis glomerata pollen, in a controlled setting, the Fraunhofer allergen challenge chamber, first without protection and then protected by HPMC or AM-301 (7 days apart). Efficacy was assessed from total nasal symptom score (TNSS), nasal secretion weight, and subjective rating. The primary endpoint was the difference, between AM-301 and HPMC, in least square mean change in TNSS over a 4-h exposure to allergen. RESULTS: The study enrolled 36 persons, and 35 completed all study visits. The mean TNSS was 5.91 (SD = 1.45) during unprotected exposure, 5.20 (SD = 1.70) during protection with HPMC, and 4.82 (SD = 1.74) during protection with AM-301. The difference in least square means between the two treatments was -0.39 (95% CI: -0.89 to 0.10), establishing the noninferiority of AM-301. No difference in mean weight of nasal secretions was observed between the treatments. Efficacy was rated as good or very good for AM-301 by 31% and for HPMC by 14% of subjects. Sixteen subjects reported adverse events with a relationship to AM-301 or HPMC; most adverse events were mild, and none was serious. DISCUSSION/CONCLUSION: AM-301 demonstrated noninferiority toward HPMC in the primary endpoint and was perceived better in subjective secondary endpoints. Both barrier-forming products had a persisting protective effect over 4 h and were safe.

Drug-Free Nasal Spray as a Barrier against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia.

The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after infection, viral titer was reduced by about 12-folds and 3-folds on Day 4. The results suggest that AM-301 is safe and significantly decelerates SARS-CoV-2 replication in cell culture inhibition assays of prophylaxis (pre-viral load application) and mitigation (post-viral load application). Its physical (non-pharmaceutical) mechanism of action, safety and efficacy warrant additional investigations both in vitro and in vivo for safety and efficacy against a broad spectrum of airborne viruses and allergens.