The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
Nikita V Lomakin, Bulat A Bakirov, Denis N Protsenko, Vadim I Mazurov, Gaziyavdibir H Musaev, Olga M Moiseeva, Elena S Pasechnik, Vladimir V Popov, Elena A Smolyarchuk, Ivan G Gordeev, Mikhail Yu Gilyarov, Darya S Fomina, Anton I Seleznev, Yulia N Linkova, Ekaterina A Dokukina, Anna V Eremeeva, Polina S Pukhtinskaia, Maria A Morozova, Arina V Zinkina-Orikhan, Anton A Lutckii
Inflammation Research, doi:10.1007/s00011-021-01507-5
Objective and design The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate.
Authors and Affiliations Nikita V. Lomakin
References
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Capra, Rossi, Mattioli, Romanelli, Scarpazza et al., Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia, Eur J Intern Med
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'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Objective and design</jats:title>\n'
' <jats:p>The aim of this double-blind, placebo-controlled, phase III CORONA '
'clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab '
'(LVL) in subjects with severe COVID-19.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Subjects</jats:title>\n'
' <jats:p>The study included 217 patients. The eligible were men and '
'non-pregnant women aged 18\xa0years or older, hospitalized for severe COVID-19 '
'pneumonia.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Treatment</jats:title>\n'
' <jats:p>206 subjects were randomized (1:1) to receive single subcutaneous '
'administration of LVL 324\xa0mg or placebo, both in combination with standard of care (SOC). '
'204 patients received allocated therapy. After the LVL/placebo administration in case of '
'deterioration of symptoms, the investigator could perform a single open-label LVL 324\xa0mg '
'administration as the rescue therapy.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>The primary efficacy endpoint was the proportion of patients with '
'sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data '
'obtained after rescue therapy administration were considered missing. For primary efficacy '
'analysis, all subjects with missing data were considered non-responders.</jats:p>\n'
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' <jats:title>Results</jats:title>\n'
' <jats:p>63.1% and 42.7% of patients in the LVL and in the placebo groups, '
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' <jats:title>Conclusion</jats:title>\n'
' <jats:p>In patients with radiologically confirmed SARS-CoV-2 pneumonia, '
'requiring or not oxygen therapy (but not ventilation) with no signs of other active infection '
'administration of LVL\u2009+\u2009SOC results in an increase of sustained clinical '
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' <jats:p>The trial is registered at the US National Institutes of Health '
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'Lancet. 2021;397(10285):1637–45.',
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'unstructured': 'Zeraatkar D, Cusano E, Martinez JPD, Qasim A, Mangala SO, Kum E, et al. '
'(2021) Tocilizumab and sarilumab alone or in combination with '
'corticosteroids for COVID-19: a systematic review and network '
'meta-analysis. medRxiv. 2021.07.05.21259867. '
'https://doi.org/10.1101/2021.07.05.21259867',
'DOI': '10.1101/2021.07.05.21259867'}],
'container-title': 'Inflammation Research',
'original-title': [],
'language': 'en',
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'issued': {'date-parts': [[2021, 9, 29]]},
'references-count': 22,
'journal-issue': {'issue': '10-12', 'published-print': {'date-parts': [[2021, 12]]}},
'alternative-id': ['1507'],
'URL': 'http://dx.doi.org/10.1007/s00011-021-01507-5',
'relation': {},
'ISSN': ['1023-3830', '1420-908X'],
'subject': ['Pharmacology', 'Immunology'],
'container-title-short': 'Inflamm. Res.',
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'name': 'received',
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{ 'value': '14 September 2021',
'order': 2,
'name': 'revised',
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{ 'value': '16 September 2021',
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'name': 'accepted',
'label': 'Accepted',
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{'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}},
{ 'value': 'The research leading to these results received funding from BIOCAD under Grant '
'Agreement No BCD-089-4/CORONA. Authors Nikita V. Lomakin, Bulat A. Bakirov, '
'Denis N. Protsenko, Vadim I. Mazurov, Gaziyavdibir H. Musaev, Olga M. Moiseeva, '
'Elena S. Pasechnik, Vladimir V. Popov, Elena A. Smolyarchuk, Ivan G. Gordeev, '
'Darya S. Fomina have no conflicts of interest to declare that are relevant to '
'the content of this article. Author Mikhail Yu. Gilyarov received a speaking '
'fee from Boehringer Ingelheim, Bayer, Pfizer и Servier. Authors Anton I. '
'Seleznev, Yulia N. Linkova, Ekaterina A. Dokukina, Polina S. Pukhtinskaia, Anna '
'V. Eremeeva, Maria A. Morozova, Arina V. Zinkina-Orikhan and Anton A. Lutckii, '
'are JSC BIOCAD employees.',
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'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}},
{ 'value': 'This study was performed in line with the principles of the Declaration of '
'Helsinki of 1964, and its later amendments and was approved by the Central '
'Regulatory Authorities of the Russian Federation (Authorization by the Ministry '
'of Healthcare of the Russian Federation No. 176 of April 22, 2020; Extract from '
'minutes of Ethics Council of Ministry of Health of The Russian Federation '
'No.216, dated 21th of April, 2020) and Ethical Review Boards of each of the '
'participating sites.',
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'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Ethical approval'}},
{ 'value': 'Informed consent was obtained from all individual participants included in the '
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'group': {'name': 'EthicsHeading', 'label': 'Consent to participate'}},
{ 'value': 'There is no identifiable information in the manuscript. Patients signed '
'informed consent which included information about publishing the analyzed data.',
'order': 5,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent to publish'}}]}
