Azelastine Nasal Spray in Non-Hospitalised Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial
Peter Meiser, Michael Flegel, Frank Holzer, Dorothea Groß, Charlotte Steinmetz, Barbara Scherer, Rajesh Jain
doi:10.20944/preprints202410.2532.v1
Availability of nasal spray treatments that inhibit the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into nose and nasopharynx at early stages can be an appropriate approach to stop or delay the progression of the disease. We performed a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicentric, phase II clinical trial comparing the rate of hospitalization due to COVID-19 infection between azelastine 0.1% nasal spray and placebo nasal spray treatment groups. The study furthermore assessed the reduction in virus load in SARS-CoV-2 infected subjects estimated via quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using nasopharyngeal swabs in both the groups during the treatment period. A total of 294 subjects with mild COVID-19 infection were screened and randomized in a 1:1 ratio. There was no incidence of COVID-19 related hospitalization in both treatment groups. Mean virus load was significantly reduced in both groups during the 11 treatment days as compared with baseline viral load values. The reduction in virus load in the azelastine 0.1% nasal spray group was significantly higher than the reduction in the placebo group at day 11 (log10 5.93 vs. log10 5.85 copies/mL, respectively, p=0.0041). A total of 39 (32.0%) subjects in the azelastine 0.1% treatment group and 40 (31.0%) subjects in the placebo group reported 48 and 51 adverse events, respectively. It is therefore concluded that azelastine 0.1% nasal spray is an efficacious, safe, and well-tolerated treatment of mild COVID-19 infection.
well as the formation of a physical barrier (HPMC is one ingredient of the formulation) might have contributed to such effects.
Conclusions Overall, no incidence of COVID-19 related hospitalization, accompanied by significant reduction in viral load and improvements in symptom severity in this study support the use of azelastine 0.1% nasal spray in subjects tested positive for SARS-CoV-2 with mild symptoms.
Supplementary Materials: The following supporting information can be downloaded at: www.mdpi.com/xxx/s1: Table S1 Funding: This research received no external funding. The Clinical Trial was funded by URSAPHARM Arzneimittel GmbH.
Institutional Review Board Statement: The study was approved by all involved Institutional Review Boards and Ethics Committees. A full list of the Institutional Review Boards and Ethics Committees involved is provided in the Supplementary Table S1 . The study was conducted in accordance with the Good Clinical Practice, the Declaration of Helsinki, and all applicable local and national regulatory requirements. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: Peter Meiser, Michael Flegel, Dorothea Groß, Charlotte Steinmetz and Barbara Scherer are employed at URSAPHARM Arzneimittel GmbH, Frank Holzer is the CEO of URSAPHARM Arzneimittel GmbH, the sponsor of the clinical trial. Rajesh Jain is employed at PharmaLex India Pvt. Ltd, the CRO which organized this trial.
References
Balasubramani, Ravichandran, Kumar Arun Prasad, Ramkumar, Shekhar et al., Spatio-Temporal Epidemiology and Associated Indicators of Covid-19 (Wave-I and Ii) in India, Sci Rep
Bernal, Jayk, Gomes Da Silva, Musungaie, Kovalchuk et al., Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, New England Journal of Medicine
Cascella, Rajnik, Features, Evaluation, and Treatment of Coronavirus (Covid-19)
Dings, Meiser, Holzer, Flegel, Selzer et al., Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on Sars-Cov-2 Viral Load and Related Symptoms in Covid-19 Patients, Pharmaceutics
Dte, Ghs, Clinical Guidance for the Syndromic Management of Suspected Covid-19 Cases
Fischhuber, Bánki, Kimpel, Kragl, Rössler et al., Antiviral Potential of Azelastine against Major Respiratory Viruses, Viruses
Ghahremanpour, Tirado-Rives, Deshmukh, Ippolito, Zhang et al., Identification of 14 Known Drugs as Inhibitors of the Main Protease of Sars-Cov-2, ACS Med Chem Lett
Jain, Mujwar, Repurposing Metocurine as Main Protease Inhibitor to Develop Novel Antiviral Therapy for Covid-19, Struct Chem
Killingley, Ben, Mann, Kalinova, Boyers et al., Safety, Tolerability and Viral Kinetics During Sars-Cov-2 Human Challenge in Young Adults, Nature Medicine
Klussmann, Peter, Grosheva, Meiser, Lehmann et al., Early Intervention with Azelastine Nasal Spray May Reduce Viral Load in Sars-Cov-2 Infected Patients, Sci Rep
Konrat, Papp, Kimpel, Rössler, Szijártó et al., The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of Sars-Cov-2 in Cell Cultures and Reconstituted Human Nasal Tissue, Front Pharmacol
Marc, Kerioui, Blanquart, Bertrand, Mitjà et al., Quantifying the Relationship between Sars-Cov-2 Viral Load and Infectiousness, eLife
Odhar, Ahjel, Albeer, Hashim, Rayshan et al., Molecular Docking and Dynamics Simulation of Fda Approved Drugs with the Main Protease from 2019 Novel Coronavirus, Bioinformation
Panahi, Mahdavi Gorabi, Talaei, Beiraghdar, Akbarzadeh et al., An Overview on the Treatments and Prevention against Covid-19, Virology Journal
Parasher, Covid-19: Current Understanding of Its Pathophysiology, Clinical Presentation and Treatment, Postgraduate Medical Journal
Reznikov, Norris, Vashisht, Bluhm, Li et al., Identification of Antiviral Antihistamines for Covid-19 Repurposing, Biochem Biophys Res Commun
Shmuel, Dalia, Tair, Yaakov, Low Ph Hypromellose (Taffix) Nasal Powder Spray Could Reduce Sars-Cov-2 Infection Rate Post Mass-Gathering Event at a Highly Endemic Community: An Observational Prospective Open Label User Survey, Expert Review of Anti-infective Therapy
Sinha, Suram, Chary, Naik, Singh et al., Efficacy and Safety of Molnupiravir in Mild Covid-19 Patients in India, Cureus
Tandon, Wu, Moore, Winchester, Tu et al., Sars-Cov-2 Accelerated Clearance Using a Novel Nitric Oxide Nasal Spray (Nons) Treatment: A Randomized Trial, The Lancet Regional Health -Southeast Asia
Winchester, John, Jabbar, John, Clinical Efficacy of Nitric Oxide Nasal Spray (Nons) for the Treatment of Mild Covid-19 Infection, Journal of Infection
Yang, Pei, Li, Ma, Zhou et al., Identification of Sars-Cov-2 Entry Inhibitors among Already Approved Drugs, Acta Pharmacol Sin
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