Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study

PLOS ONE RESEARCH ARTICLE Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study B. Fredrik Lindberg1☯, Ida Nelson ID2☯*, Jonas Ranstam ID3☯, Donald K. Riker4☯ a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 AGB-Pharma AB, Lund, Sweden, 2 Enzymatica AB, Lund, Sweden, 3 Mdas AB, Ystad, Sweden, 4 On Point Advisors, LLC, Scottsdale, AZ, United States of America ☯ These authors contributed equally to this work. * Abstract OPEN ACCESS Background Citation: Lindberg BF, Nelson I, Ranstam J, Riker DK (2023) Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study. PLoS ONE 18(1): e0279204. https://doi.org/ 10.1371/journal.pone.0279204 Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load. Editor: Walid Kamal Abdelbasset, Prince Sattam Bin Abdulaziz University, College of Applied Medical Sciences, SAUDI ARABIA Methods and findings Received: June 20, 2022 Accepted: November 29, 2022 Published: January 18, 2023 Copyright: © 2023 Lindberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The study was funded by Enzymatica AB. All authors, including the funders, participated in study design, preparation of the manuscript and decision to publish. Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: F.L. was employed This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson’s symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment. Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years. There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting PLOS ONE | https://doi.org/10.1371/journal.pone.0279204 January 18, 2023 1 / 14 PLOS ONE by Enzymatica AB when the study was conducted. Current affiliation for F.L. is AGB-Pharma AB, 222 20 Lund, Sweden. F.L. owns shares in Enzymatica and has a patent pending. I.N is employed by and owns shares in Enzymatica AB. J.R. and D.R. have provided ad hoc consultancy services and have received payment from Enzymatica AB for services rendered as their only form of compensation. J.R. was contracted as an independent statistical consultant. D.R. was contracted as an independent scientific advisor. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ColdZyme mouth spray in self-diagnosed common cold the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects’ assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study. Conclusion The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds. Introduction The common cold is a self-limiting upper respiratory viral infection affecting the individual and also the society in its high costs and lost productivity [1,2]. The common cold is caused by infection by one of over 200 known respiratory viruses, primarily rhinoviruses, but also coronaviruses, influenza viruses, adenoviruses, parainfluenza viruses, respiratory syncytial viruses and enteroviruses [3]. Rhinovirus is well adapted to its host, initially overcoming epithelial barriers, interferon release and adaptive immune responses in the nasal and throat mucosa. The diversity of viral pathogens has so far complicated the attempts to find a universal treatment [4–6]. After infection virus is usually transported from the nose back to the pharynx where infection of the mucosa is first established, followed by anterior spread [7]. The described migration of the virus finds support in the course of local symptom development, starting with sore scratchy throat and malaise, quickly followed by nasal congestion, rhinorrhea, sneezing and finally cough [8]. Thus, the first opportunity to halt local virus propagation is during the incubation period. There are few approved products designed to intervene early in common upper respiratory viral infections involving the posterior oral-pharyngeal cavity. A technology has been developed consisting of a hyperosmotic glycerol solution containing cold-adapted trypsin from the Atlantic cod to treat and alleviate the common cold [9]. When the medical device, ColdZyme, is sprayed orally, the solution forms a barrier on the pharynx that acts osmotically while at the same time interfering with viral attachment and entry. The spray solution has demonstrated broad virucidal activity in vitro resulting in a decline of 64–100% of virus activity when assaying influenza virus, rhinovirus, adenovirus and corona virus, including SARS-CoV-2, using a cytopathic host cell incubation test [10–12]. In a double-blind study on healthy volunteers inoculated (...truncated)