{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:23:42Z","timestamp":1792715022603,"version":"4.5.0"},"reference-count":29,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19pc0101038"],"award-info":[{"award-number":["JP19pc0101038"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,8,26]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I\/II study in patients with systemic lupus erythematosus (SLE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200\u2009mg; n=8\u2009or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% (3\/8 patients) for 100\u2009mg; 77.8% (7\/9 patients) for 200\u2009mg) and 66.7% (6\/9 patients) in the placebo group. No Common Terminology Criteria for Adverse Events\u2265Grade 3 TEAEs occurred. PK parameters were similar to these in previous phase I studies in healthy adults. The IGS and levels of proinflammatory cytokines after ex-vivo challenge with a Toll-like receptor 7\/8 agonist were immediately decreased by E6742 treatment. The response rate of the British Isles Lupus Assessment Group-based Composite Lupus Assessment at week 12 was 37.5% (3\/8 patients) for E6742 100\u2009mg, 57.1% (4\/7 patients) for E6742 200\u2009mg and 33.3% (3\/9 patients) for placebo group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>E6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05278663\">NCT05278663<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004701","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T21:50:25Z","timestamp":1726609825000},"page":"e004701","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first in patient, randomised, double-blind, phase I\/II study in systemic lupus erythematosus"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct05278663","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"first","affiliation":[{"name":"University of Occupational and Environmental Health, Japan, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kumanogoh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Graduate School of Medicine, Department of Respiratory Medicine and Clinical Immunology, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-962X","authenticated-orcid":false,"given":"Tatsuya","family":"Atsumi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology, and Nephrology, Hokkaido University, Sapporo, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-5824","authenticated-orcid":false,"given":"Tomonori","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Miyagi, Japan"},{"name":"Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-2244","authenticated-orcid":false,"given":"Fumitoshi","family":"Tago","sequence":"additional","affiliation":[{"name":"Eisai Co Ltd, Bunkyo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7145-9125","authenticated-orcid":false,"given":"Mari","family":"Aoki","sequence":"additional","affiliation":[{"name":"Eisai Co Ltd, Bunkyo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0244-5385","authenticated-orcid":false,"given":"Shintaro","family":"Yamamuro","sequence":"additional","affiliation":[{"name":"Eisai Co Ltd, Bunkyo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Osaka University Immunology Frontier Research Center, Suita, Osaka, 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