{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:10Z","timestamp":1791065290160,"version":"4.1.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Technology &amp; Therapeutics"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Iscalimab is a fully human, monoclonal anti-CD40 antibody that blocks CD154-induced CD40 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>In a Phase 2 (2a) study, new-onset stage 3 type 1 diabetes mellitus (T1DM) participants were randomized 2:1 to iscalimab or placebo administered as a single intravenous dose followed by weekly subcutaneous injections for 1 year to evaluate safety and effects on \u03b2 cell function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      At 14 centers in 6 countries, 44 participants (29 M\/15 F, mean age 16 years [range 12\u201321 years]) were randomized; 39 completed the study (26 active:13 placebo). Treatment was discontinued prematurely in seven, two of these due to a temporary trial halt during the COVID-19 pandemic. No difference in C-peptide area under the curve (C-peptide\n                      <jats:sub>(AUC)<\/jats:sub>\n                      ) during a mixed meal tolerance test was observed after 52 weeks (ratio active:placebo 1.173 [80% confidence interval (CI) 0.94, 1.47],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>(one-sided)<\/jats:sub>\n                      = 0.18). The yearly rate of change of normalized stimulated C-peptide\n                      <jats:sub>(AUC)<\/jats:sub>\n                      suggests a slower decline of \u03b2 cell function: iscalimab \u22120.14 (80% CI \u22120.23, \u22120.05) versus placebo \u22120.33 (\u22120.42, \u22120.23) nmol\/L per year (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>(one-sided)<\/jats:sub>\n                      = 0.04). The estimated geometric mean ratio to baseline of hemoglobin A1c at week 52 was lower with iscalimab than placebo (0.95 [80% CI 0.92\u20130.99] versus 1.05 [80% CI 1.00\u20131.11], respectively). Leukocytes, neutrophils, and monocytes were lower, whereas T and B lymphocytes were higher in iscalimab-treated participants compared with placebo. Iscalimab was generally safe and well tolerated. Five serious adverse events (AEs) occurred under iscalimab (urinary tract infection, diabetic metabolic decompensation, traumatic fracture, hypoglycemia, and large intestine infection [3.4% each]) and one under placebo (mastoiditis [6.7%]). The most common AEs were hypoglycemia, nasopharyngitis, injection site reaction, COVID-19, and neutropenia. The majority of AEs were mild-to-moderate in intensity and resolved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Iscalimab has an acceptable safety and tolerability profile. The sample size limits interpretation of efficacy results. CD40:CD154 inhibition warrants further investigation in T1DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15209156251396115","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T07:01:07Z","timestamp":1763708467000},"page":"550-563","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["A Phase 2 (2a) Randomized Trial of Iscalimab in Adolescents and Young Adults with New-Onset Type 1 Diabetes"],"prefix":"10.1177","volume":"28","author":[{"given":"Chantal","family":"Mathieu","sequence":"first","affiliation":[{"name":"UZ Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Advanced Quantitative Sciences, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Wagner","sequence":"additional","affiliation":[{"name":"Clinical Science and Innovation, Novartis Biomedical Research, East Hanover, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Kompa","sequence":"additional","affiliation":[{"name":"Regulatory Affairs, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Biomarker Development, Novartis BioMedical Research, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Biomarker Development, Novartis BioMedical Research, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hinder","sequence":"additional","affiliation":[{"name":"Translational Medicine, Novartis Biomedical Research, Postfach, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Translational Medicine, Novartis Biomedical Research, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison B.","family":"Goldfine","sequence":"additional","affiliation":[{"name":"Translational Medicine, Novartis Biomedical Research, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the CFZ533X2207 Study Team and the INNODIA 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