Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial
Background The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.Methods Part 2 was a randomised, double-blind phase 2 study (NCT04402866)...
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BMJ Publishing Group
2023-07-01
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| Series: | BMJ Open Respiratory Research |
| Online Access: | https://bmjopenrespres.bmj.com/content/10/1/e001627.full |
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| author | Tuan Nguyen Jacky Woo Rajeev Saggar Nathan D Pfeifer David A Lombardi Brett Haumann John Belperio Maxim Bogus Valentyn Moskalenko David L Bourdet Elad Kaufman Corbin G Thompson Edmund J Moran |
| author_facet | Tuan Nguyen Jacky Woo Rajeev Saggar Nathan D Pfeifer David A Lombardi Brett Haumann John Belperio Maxim Bogus Valentyn Moskalenko David L Bourdet Elad Kaufman Corbin G Thompson Edmund J Moran |
| author_sort | Tuan Nguyen |
| collection | DOAJ |
| description | Background The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.Methods Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18–80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint.Results Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile.Conclusions Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19. |
| format | Article |
| id | doaj-art-905da654e8a64ea59f91db7bc7d56b1d |
| institution | DOAJ |
| issn | 2052-4439 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Respiratory Research |
| spelling | doaj-art-905da654e8a64ea59f91db7bc7d56b1d2025-08-20T03:02:02ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392023-07-0110110.1136/bmjresp-2023-001627Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trialTuan Nguyen0Jacky Woo1Rajeev Saggar2Nathan D Pfeifer3David A Lombardi4Brett Haumann5John Belperio6Maxim Bogus7Valentyn Moskalenko8David L Bourdet9Elad Kaufman10Corbin G Thompson11Edmund J Moran12Theravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma UK Limited, London, UKRonald Reagan UCLA Medical Center, Los Angeles, California, USAArensia Exploratory Medicine SRL, Chișinău, Moldova (the Republic of)Arensia Exploratory Medicine, LLC, Kyiv City Clinical Hospital #12, Oleksandrivska Kyiv City Clinical Hospital, Kyiv, UkraineTheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USATheravance Biopharma Inc, South San Francisco, California, USABackground The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.Methods Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18–80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint.Results Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile.Conclusions Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.https://bmjopenrespres.bmj.com/content/10/1/e001627.full |
| spellingShingle | Tuan Nguyen Jacky Woo Rajeev Saggar Nathan D Pfeifer David A Lombardi Brett Haumann John Belperio Maxim Bogus Valentyn Moskalenko David L Bourdet Elad Kaufman Corbin G Thompson Edmund J Moran Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial BMJ Open Respiratory Research |
| title | Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial |
| title_full | Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial |
| title_fullStr | Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial |
| title_full_unstemmed | Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial |
| title_short | Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial |
| title_sort | efficacy and safety of an inhaled pan janus kinase inhibitor nezulcitinib in hospitalised patients with covid 19 results from a phase 2 clinical trial |
| url | https://bmjopenrespres.bmj.com/content/10/1/e001627.full |
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