{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:01:47Z","timestamp":1790341307353,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first\u2010in\u2010Japanese double\u2010blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70\u00a0mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90\u2010day follow\u2010up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose\u2010dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).<\/jats:p>","DOI":"10.1002\/cpdd.70097","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:01:24Z","timestamp":1788948084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A First\u2010in\u2010Japanese Phase 1, Double\u2010Blind, Placebo\u2010Controlled, Parallel\u2010Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants"],"prefix":"10.1002","volume":"15","author":[{"given":"Takakazu","family":"Sato","sequence":"first","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Fukase","sequence":"additional","affiliation":[{"name":"Clinical Research Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arisa","family":"Karasawa","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2025.152876"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000072"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13663"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136094"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044145"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00926-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13172"},{"key":"e_1_2_11_9_1","first-page":"942","article-title":"Inherited kidney complement diseases","volume":"14","author":"Mathieu L","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8720"},{"key":"e_1_2_11_11_1","first-page":"S41","article-title":"Local tissue complement synthesis \u2013 fine tuning a blunt instrument","volume":"49","author":"Marsh JE","year":"2001","journal-title":"Arch Immunol Ther Exp"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603420103"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.690821"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812584106"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1537974"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410316"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.37349\/ei.2024.00161"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2025.11.017"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2018.0753"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.11.1419"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)35315-7"},{"key":"e_1_2_11_22_1","unstructured":"ClinicalTrials.gov.A study to evaluate the efficacy and safety of sefaxersen (RO7434656) in participants with primary immunoglobulin A (IgA) nephropathy at high risk of progression (IMAGINATION). ClinicalTrials.gov identifier: NCT05797610. Accessed October 5 2025.https:\/\/clinicaltrials.gov\/study\/NCT05797610"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2024.02.303"},{"key":"e_1_2_11_24_1","unstructured":"ClinicalTrial.gov.A study to evaluate the effectiveness and safety of IONIS\u2010FB\u2010LRx an antisense inhibitor of complement factor B in adult participants with primary IgA nephropathy. ClinicalTrials.gov identifier: NCT04014335. Accessed October 5 2025.https:\/\/clinicaltrials.gov\/study\/NCT04014335"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaf116.0244"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01870"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13143"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00028-4"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:40:28Z","timestamp":1790340028000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cpdd.70097"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70097","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2025-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70097"}}