{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:21:53Z","timestamp":1783383713867,"version":"3.54.6"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fenebrutinib is a Bruton's tyrosine kinase inhibitor under investigation for the treatment of multiple sclerosis. The goal of this study was to investigate the effect of fenebrutinib on cardiac repolarization (QT interval) as well as its safety, tolerability, and pharmacokinetics in healthy participants. Part A was a randomized, double\u2010blind, placebo\u2010controlled, single\u2010ascending dose study of therapeutic (400\u2009mg) and supratherapeutic (700\u2009mg) doses of fenebrutinib. Part B was a randomized, double\u2010blind, single\u2010dose, four\u2010way crossover study that included both therapeutic and supratherapeutic fenebrutinib doses, a positive control (moxifloxacin 400\u2009mg), and placebo. The QT interval was corrected for heart rate using the Fridericia formula (QTcF). Part A (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916) showed that both doses were well tolerated, with no serious adverse events (AEs), AEs of special interest, or Grade \u2265\u20092 AEs. In Part B (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200985), all upper bounds (UBs) of one\u2010sided 95% confidence intervals (CIs) for the least squares mean placebo\u2010adjusted \u0394QTcF (\u0394\u0394QTcF) values were\u2009&lt;\u200910\u2009ms; maximum observed values were 5.3 and 8.2\u2009ms at 1\u2009h after the therapeutic and supratherapeutic doses, respectively. All predefined timepoints after moxifloxacin administration had a 99% CI lower bound of \u0394\u0394QTcF of &gt;\u20095\u2009ms, which confirmed assay sensitivity. In the regression analysis, UBs of one\u2010sided 95% CIs for \u0394\u0394QTcF at the maximum concentration of fenebrutinib were\u2009&lt;\u200910\u2009ms: 4.4 and 7.8\u2009ms with the therapeutic and supratherapeutic doses, respectively. Overall, both doses of fenebrutinib had no clinically meaningful impact on QT interval and were well tolerated, supporting fenebrutinib's favorable safety profile and continued clinical development.\n                  <\/jats:p>","DOI":"10.1111\/cts.70518","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:37:07Z","timestamp":1772987827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fenebrutinib and Effect on the\n                    <scp>QT<\/scp>\n                    \/\n                    <scp>QTc<\/scp>\n                    Interval in Healthy Participants"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4732","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"first","affiliation":[{"name":"Genentech Inc.  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San Francisco California USA"},{"name":"Department of Biological and Environmental Engineering Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0041-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007035"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001262"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00289-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00063-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028936"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-022-01229-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2001\/28962"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0779-z"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1056"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01712"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.662223"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03267-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00174-7"},{"key":"e_1_2_10_16_1","unstructured":"ClinicalTrials.gov \u201cA Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance) \u201daccessed September 2 2025 https:\/\/clinicaltrials.gov\/study\/NCT04586010."},{"key":"e_1_2_10_17_1","unstructured":"ClinicalTrials.gov \u201cStudy to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance2) \u201daccessed September 2 2025 https:\/\/clinicaltrials.gov\/study\/NCT04586023."},{"key":"e_1_2_10_18_1","unstructured":"ClinicalTrials.gov \u201cA Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis (FENtrepid) \u201daccessed September 2 2025 https:\/\/clinicaltrials.gov\/study\/NCT04544449."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007938"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28104225"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.96.15_supplement.4564"},{"issue":"7","key":"e_1_2_10_22_1","article-title":"The Safety Profile of Fenebrutinib in Patients With Multiple Sclerosis Is Consistent With Those in Previously Studied Autoimmune Indications","volume":"102","author":"Oh J.","year":"2024","journal-title":"Neurology"},{"key":"e_1_2_10_23_1","unstructured":"US Food and Drug Administration \u201cE14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs \u201d(2005) https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e14\u2010clinical\u2010evaluation\u2010qtqtc\u2010interval\u2010prolongation\u2010and\u2010proarrhythmic\u2010potential\u2010non\u2010antiarrhythmic\u20100."},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543400802020938"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3471-x"},{"key":"e_1_2_10_26_1","volume-title":"Calquence (Acalabrutinib). 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