Demonstration of a Decongestant Effect of Coldamaris Akut Compared to Saline Nasal Spray in Participants Suffering from Seasonal Allergic Rhinitis

Purpose: Carrageenan-containing nasal sprays are known to alleviate symptoms of common cold and allergic symptoms by building a barrier against airborne intruders. The objective of this study was to develop a hyperosmolar nasal spray with barrier-forming properties and to demonstrate its decongestant effect in the context of allergic rhinitis. Methods: The efficacy of the nasal spray components was first demonstrated in vitro by a virus replication inhibition, water absorption, and barrier assay. Clinical efficacy was assessed in a randomized, controlled, crossover trial, where adults with a history of severe seasonal allergic rhinitis were exposed to grass pollen allergens under controlled conditions for a total of 6 hours. Participants received either the carrageenan- and sorbitol containing nasal spray (CS) or saline solution (SS) after 1h45min of allergen exposure. After one week, participants repeated the exposure, receiving the treatment (CS or SS) they had not received before. The primary efficacy endpoint was the mean change in 'Nasal Congestion Symptom Score' (NCSS) during the allergen exposure. Secondary efficacy endpoints were nasal airflow, nasal secretion, total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total respiratory symptom score (TRSS). Results: Preclinical assays showed virus-blocking, barrier building and water withdrawing properties of the CS components. In the clinical study, a total of 46 participants were screened, 41 were randomized and 39 completed the study. There was no significant difference in mean NCSS change from pre- to post-treatment between CS and SS (mean difference of 0.02 [95% CI -0.19; 0.24] during the first 2 hours after treatment) when analyzed by intention-to-treat. However, nasal airflow increased over time after treatment with CS, while it declined after SS, leading to a growing difference in airflow between CS- and SS-treated participants (p=0.039 at 6:00h). The anterior nasal airflow increased after treatment in 23/38 (61%) of the CS treated participants, compared to only 13/38 (34%) of the SS treated participants (p=0.024). The mean nasal secretion over 2-6 h was reduced by 1.00 g or -25% after CS (p=0.003) compared to pre-treatment, while it was reduced by only -0.50 g after SS (p=0.137). No significant differences in TNSS, TOSS and TRSS were observed between CS and SS treatments. Conclusion: CS builds a barrier at the mucosa against viruses and dust and is safe and effective in alleviating nasal congestion, nasal airflow and nasal secretion in adults with grass pollen allergy. ### Competing Interest Statement NU, MM, HD and EP are employees of Marinomed Biotech AG. MS received consulting fees from Marinomed Biotech AG. The other authors have no competing interests in this work. This manuscript is also available at medRxiv preprint server. ### Clinical Trial NCT04532762 ### Funding Statement This study was funded by Marinomed Biotech AG. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the City of Vienna oversaw trial conduct and documentation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors