RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial

{ 'indexed': {'date-parts': [[2024, 5, 7]], 'date-time': '2024-05-07T00:33:18Z', 'timestamp': 1715041998627}, 'reference-count': 31, 'publisher': 'MDPI AG', 'issue': '3', 'license': [ { 'start': { 'date-parts': [[2024, 5, 6]], 'date-time': '2024-05-06T00:00:00Z', 'timestamp': 1714953600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/100004440', 'name': 'joint Welcome Trust and Royal Society', 'doi-asserted-by': 'publisher', 'award': ['206579/Z/17/Z']}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Enisamium is an orally available therapeutic that inhibits influenza A virus and ' 'SARS-CoV-2 replication. We evaluated the clinical efficacy of enisamium treatment combined ' 'with standard care in adult, hospitalized patients with moderate COVID-19 requiring external ' 'oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly ' 'assigned to receive either enisamium (500 mg per dose, four times a day) or a placebo. The ' 'primary outcome was an improvement of at least two points on an eight-point severity rating ' '(SR) scale within 29 days of randomization. We initially set out to study the effect of ' 'enisamium on patients with a baseline SR of 4 or 5. However, because the study was started ' 'early in the COVID-19 pandemic, and COVID-19 had been insufficiently studied at the start of ' 'our study, an interim analysis was performed alongside a conditional power analysis in order ' 'to ensure patient safety and assess whether the treatment was likely to be beneficial for one ' 'or both groups. Following this analysis, a beneficial effect was observed for patients with ' 'an SR of 4 only, i.e., patients with moderate COVID-19 requiring supplementary oxygen. The ' 'study was continued for these COVID-19 patients. Overall, a total of 592 patients were ' 'enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 ' 'were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 ' '(50.2%) to the placebo group. An analysis of the population showed that if patients were ' 'treated within 4 days of the onset of COVID-19 symptoms (n = 33), the median time to ' 'improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.005). ' 'For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median ' 'time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p ' '= 0.002). Our findings suggest that enisamium is safe to use with COVID-19 patients, and that ' 'the observed clinical benefit of enisamium is worth reporting and studying in ' 'detail.</jats:p>', 'DOI': '10.3390/arm92030021', 'type': 'journal-article', 'created': {'date-parts': [[2024, 5, 6]], 'date-time': '2024-05-06T19:09:36Z', 'timestamp': 1715022576000}, 'page': '202-217', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, ' 'Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial', 'prefix': '10.3390', 'volume': '92', 'author': [ { 'given': 'Olga', 'family': 'Holubovska', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Infectious Diseases, O.O. Bogomolets National ' 'Medical University, T. Shevchenko Blvd. 13, 01601 Kyiv, ' 'Ukraine'}]}, { 'given': 'Pavlo', 'family': 'Babich', 'sequence': 'additional', 'affiliation': [{'name': 'State Expert Center, Smolenska Str. 10, 03057 Kyiv, Ukraine'}]}, { 'ORCID': 'http://orcid.org/0000-0002-2630-1827', 'authenticated-orcid': False, 'given': 'Alla', 'family': 'Mironenko', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Respiratory and Other Viral Infections, L.V. ' 'Gromashevsky Institute of Epidemiology and Infectious Diseases ' 'of the NAMS of Ukraine, Amosova Str. 5a, 03083 Kyiv, Ukraine'}]}, { 'given': 'Jens', 'family': 'Milde', 'sequence': 'additional', 'affiliation': [ { 'name': 'Pharmalog Institut für Klinische Forschung GmbH, ' 'Oskar-Messter-Str. 29, 85737 Ismaning, Germany'}]}, { 'given': 'Yuriy', 'family': 'Lebed', 'sequence': 'additional', 'affiliation': [{'name': 'Pharmaxi LLC, Filatova Str. 10A, 01042 Kyiv, Ukraine'}]}, { 'given': 'Holger', 'family': 'Stammer', 'sequence': 'additional', 'affiliation': [ { 'name': 'Pharmalog Institut für Klinische Forschung GmbH, ' 'Oskar-Messter-Str. 29, 85737 Ismaning, Germany'}]}, { 'ORCID': 'http://orcid.org/0000-0002-3633-1309', 'authenticated-orcid': False, 'given': 'Lutz', 'family': 'Mueller', 'sequence': 'additional', 'affiliation': [{'name': 'Regenold GmbH, Zöllinplatz 4, 79410 Badenweiler, Germany'}]}, { 'given': 'Aartjan J. W.', 'family': 'te Velthuis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Biology, Princeton University, ' 'Princeton, NJ 08544, USA'}, { 'name': 'Division of Virology, Department of Pathology, University of ' 'Cambridge Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK'}]}, { 'given': 'Victor', 'family': 'Margitich', 'sequence': 'additional', 'affiliation': [ { 'name': 'Farmak Joint Stock Company, Kyrylivska Str., 04080 Kyiv, ' 'Ukraine'}]}, { 'given': 'Andrew', 'family': 'Goy', 'sequence': 'additional', 'affiliation': [ { 'name': 'Farmak Joint Stock Company, Kyrylivska Str., 04080 Kyiv, ' 'Ukraine'}]}], 'member': '1968', 'published-online': {'date-parts': [[2024, 5, 6]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '536', 'DOI': '10.1038/s41564-020-0695-z', 'article-title': 'The Species Severe Acute Respiratory Syndrome-Related Coronavirus: ' 'Classifying 2019-nCoV and Naming It SARS-CoV-2', 'volume': '5', 'author': 'Gorbalenya', 'year': '2020', 'journal-title': 'Nat. 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