{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:56:51Z","timestamp":1781647011024,"version":"3.54.5"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"MediciNova, Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pulm Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>MN-166 (ibudilast) is an orally available small molecule drug candidate that inhibits macrophage migration inhibitory factor and phosphodiesterase 4 and 10. The rationale for using MN-166 to prevent Acute Respiratory Failure (ARF) is based upon its cellular and molecular target actions and recent research in LPS-induced ARF animal model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this double-blind, randomized (1:1), placebo-controlled study conducted at two centers in the United States, we evaluated MN-166 (100\u00a0mg\/day: 50\u00a0mg twice daily for 7 days) compared to placebo in hospitalized participants with COVID-19 at risk for ARF. The study\u2019s co-primary endpoints were the proportion of participants free of respiratory failure at Day 7 and the proportion of participants with at least a one-point clinical status improvement in the National Institute of Allergy and Infectious Diseases 8-point ordinal scale at Day 7. All randomized participants received a study drug and were evaluated for efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 34 participants were randomly assigned to either MN-166 or placebo (17 in each treatment group). The study achieved one of the co-primary endpoints, a statistically significant difference (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.02) between groups related to the proportion of participants free from respiratory failure. Two-fold of participants in the MN-166 treatment group were free from respiratory failure on Day 7 versus the placebo group (70.6% vs. 35.3%; percentage difference: 35.3% [95% CI: 1.98 to 59.46];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.02). Sensitivity analysis showed similar differences among participants receiving interleukin-6 antibody therapy, with a statistically significant percentage difference from the placebo group (71.4% vs. 25%; 46.4%, 95% CI: 1.48 to 91.38,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). MN 166 treatment was better tolerated than placebo. Two deaths were reported in the placebo group and none in the MN-166 treatment group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MN-166 treatment was associated with faster recovery from respiratory failure in participants with COVID-19, independent of interleukin-6 antibody therapy. MN-166 was well-tolerated with fewer adverse events compared to placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04429555, Registered 11 June 2020,<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12890-026-04261-8","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:17:11Z","timestamp":1775139431000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of MN-166 (ibudilast) on acute respiratory failure prevention in hospitalized participants with COVID-19: a randomized, double-blind, placebo-controlled phase 2 study"],"prefix":"10.1186","volume":"26","author":[{"given":"David L.","family":"Wyles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Iwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelia","family":"Klonowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"4261_CR1","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1001\/jama.2012.5669","volume":"307","author":"VM Ranieri","year":"2012","unstructured":"Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. 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The following Institutional Review Boards approved all study documents and amendments before the clinical study began: (1) Colorado Multiple Institutional Review Board, CB F490, University of Colorado, CO, USA for the study site Denver Health and Hospital Authority, Denver, CO, USA, and (2) Human Research Protection Program Institutional Review Boards, New Haven CT for the study site Yale New Haven Hospital, Saint Raphael\u2019s Campus, New Haven, CT, USA. We obtained informed consent from all the participants of this study and documented in line with regulatory requirements and GCP principles before any clinical study-specific procedure was initiated.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KM and YI are the employees of MediciNova, Inc. EK is a contact employee with MediciNova, Inc. DLW is the Principal Investigator of this clinical trial.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"218"}}