{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:13:50Z","timestamp":1789172030712,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin\u2010producing pancreatic \u03b2\u2010cells. Preserving remaining \u03b2\u2010cells at the time of diagnosis may improve long\u2010term outcomes. Frexalimab is a humanised monoclonal antibody specific for CD40L undergoing evaluation for treatment of various immune\u2010mediated conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Analysis<\/jats:title>\n                    <jats:p>\n                      This is a double\u2010blind, Phase 2 trial to assess the efficacy and safety of frexalimab for preservation of pancreatic \u03b2\u2010cell function in adolescents and young adults (12\u201335\u2009years) with recently diagnosed Stage 3 T1D on insulin therapy. Participants who meet all inclusion criteria will be randomly assigned to receive frexalimab or a matching placebo in a 2:1 ratio in all cohorts for 104\u2009weeks. A total of 192 participants will be recruited sequentially into two parts. Part A (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930) is exploratory and designed to establish the safety of the highest dose of frexalimab compared with placebo in adults (18\u201335\u2009years). In Part B, 162 adolescents and young adults (12\u201321\u2009years) are randomised sequentially to three age\u2010adjusted dose\u2010levels of frexalimab or placebo. The primary endpoint is the change from baseline to 52\u2009weeks in mean 2\u2010h mixed meal tolerance test stimulated C\u2010peptide concentration, calculated from the area under the curve. Secondary endpoints include time in range by intermittent continuous glucose monitoring measures, glycated haemoglobin (HbA1c), daily insulin dose, number of hypoglycaemic events and insulin dose adjusted HbA1c measurements.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and Dissemination<\/jats:title>\n                    <jats:p>This trial received ethical approval in October 2023 and began screening in December 2023 with first participant randomised in January 2024. The results will be submitted to a peer\u2010reviewed medical journal and presented at conferences.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial registration:<\/jats:bold>\n                      EU trial number:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/euclinicaltrials.eu\/search-for-clinical-trials\/?lang=en&amp;EUCT=2022-500531-36-00\">2022\u2010500531\u201036\u201000<\/jats:ext-link>\n                      and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      :\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06111586\">NCT06111586<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70785","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:10:59Z","timestamp":1779927059000},"page":"6584-6594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 2 Trial of Frexalimab, a\n                    <scp>CD40L<\/scp>\n                    Antagonist, in Adolescents and Adults With Recent\u2010Onset Type 1 Diabetes (\n                    <scp>FABULINUS<\/scp>\n                    ): Rationale and Study Design"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-6983","authenticated-orcid":false,"given":"Andriy","family":"Cherkas","sequence":"first","affiliation":[{"name":"Sanofi  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Rotthaeuser","sequence":"additional","affiliation":[{"name":"Sanofi  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-2405","authenticated-orcid":false,"given":"Niels","family":"Porksen","sequence":"additional","affiliation":[{"name":"Sanofi  Frankfurt Germany"},{"name":"Independent Consultant  R\u00f8nde Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Labard","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4791-3996","authenticated-orcid":false,"given":"My\u2010Li\u00ean","family":"Nguy\u00ean\u2010Pascal","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Coudert","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Berthou","sequence":"additional","affiliation":[{"name":"Biostatistician, IT&amp;M Stats for Sanofi  Neuilly\u2010sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0340-9752","authenticated-orcid":false,"given":"Marie","family":"Baccara\u2010Dinet","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4427-9507","authenticated-orcid":false,"given":"Gabor","family":"Boka","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-3513","authenticated-orcid":false,"given":"Mark","family":"Peakman","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-6706","authenticated-orcid":false,"given":"Felix","family":"Reschke","sequence":"additional","affiliation":[{"name":"Centre for Diabetes and Endocrinology Children's Hospital Auf der Bult  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-1824","authenticated-orcid":false,"given":"Michael J.","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Florida Diabetes Institute, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101565"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1297\/cpe.28.43"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.1.250"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20100360"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(22)00218\u20102"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098\u2010024\u201001310\u20102"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.25040\/ntsh2023.01.04"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14572"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci143683"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.12.005"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1160\/th04\u201012\u20100774"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903888"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309439"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19\u20100057"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18\u20100494"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2006136"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308743"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306691"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20101538"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13153"},{"key":"e_1_2_17_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci120555"},{"key":"e_1_2_17_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15\u20101615"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010020\u201005115\u20106"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010024\u201006124\u20105"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(11)60931\u20108"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13\u20100236"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13\u20100345"},{"key":"e_1_2_17_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23\u2010S002"},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07\u20102451"},{"key":"e_1_2_17_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.5.1245"},{"key":"e_1_2_17_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12\u20102480"},{"key":"e_1_2_17_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20102215"},{"key":"e_1_2_17_34_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23\u2010S006"},{"key":"e_1_2_17_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17\u20102707"},{"key":"e_1_2_17_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.20.5.760"},{"key":"e_1_2_17_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464\u20105491.2011.03434.x"},{"key":"e_1_2_17_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296815583506"},{"key":"e_1_2_17_39_1","first-page":"111","volume-title":"Handbook of Psychology and Diabetes: A Guide to Psychological Measurement in Diabetes Research and Practice","author":"Bradley C.","year":"1994"},{"issue":"1","key":"e_1_2_17_40_1","article-title":"Development of the Diabetes Treatment Satisfaction Questionnaire (DTSQ) for Teenagers and Parents: The DTSQ\u2010Teen and the DTSQ\u2010Parent (Abstract 1013)","volume":"52","author":"Bradley C.","year":"2009","journal-title":"Diabetologia"},{"key":"e_1_2_17_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08\u20101987"},{"key":"e_1_2_17_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026471"},{"key":"e_1_2_17_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2020.100641"},{"key":"e_1_2_17_44_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010128\u20107\u2010199804010\u201000001"},{"key":"e_1_2_17_45_1","unstructured":"European Medicines Agency \u201cGuideline on Clinical Investigation of Medicinal Products in the Treatment or Prevention of Diabetes Mellitus \u201d CPMP\/EWP\/1080\/00 Rev. 2 June 22 2023 https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/guideline\u2010clinical\u2010investigation\u2010medicinal\u2010products\u2010treatment\u2010or\u2010prevention\u2010diabetes\u2010mellitus\u2010revision\u20102_en.pdf."}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70785","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.70785","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:47:03Z","timestamp":1789170423000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.70785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/dom.70785"],"URL":"https:\/\/doi.org\/10.1111\/dom.70785","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.70785\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70785\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70785\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70785\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70785\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70785\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"2025-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}