{"id":62937,"date":"2026-04-29T12:00:00","date_gmt":"2026-04-29T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/first-in-human-phase-1-randomized-double-blind-placebo-controlled-study-of-tnx-1500-an-fc-modified-anti-cd154-monoclonal-antibody-evaluating-the-safety-tolerability-pharmacokinetics-and-pharm\/"},"modified":"2026-04-29T12:00:00","modified_gmt":"2026-04-29T10:00:00","slug":"first-in-human-phase-1-randomized-double-blind-placebo-controlled-study-of-tnx-1500-an-fc-modified-anti-cd154-monoclonal-antibody-evaluating-the-safety-tolerability-pharmacokinetics-and-pharm","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/first-in-human-phase-1-randomized-double-blind-placebo-controlled-study-of-tnx-1500-an-fc-modified-anti-cd154-monoclonal-antibody-evaluating-the-safety-tolerability-pharmacokinetics-and-pharm\/","title":{"rendered":"First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults"},"content":{"rendered":"<div>\n<p><b>J Clin Immunol<\/b>. 2026 Apr 29. doi: 10.1007\/s10875-026-02028-8. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Blocking CD154 (CD40L) has the potential to prolong transplanted solid organ graft survival and treat autoimmune diseases. However, first-generation anti-CD154 IgG1 monoclonal antibodies (mAbs) were associated with an increased risk of thrombosis linked to Fc binding to Fc\u03b3RIIa (CD32A). Here, we describe a first-in-human, phase 1 clinical trial of TNX-1500, a novel Fc-modified IgG4 anti-CD154 mAb designed to decrease binding to Fc\u03b3RIIa. Healthy volunteers (N = 26) were enrolled into single-ascending dose (3, 10, and 30 mg\/kg) cohorts and received TNX-1500 intravenously. TNX-1500 was generally well tolerated. Among participants receiving TNX-1500 3, 10, and 30 mg\/kg, 1 (25%), 3 (38%), and 3 (38%) participants, respectively, reported \u2265 1 treatment-emergent adverse event; all were mild or moderate in severity, and none resulted in study discontinuation. There were no thromboembolic events. Pharmacokinetic analyses of TNX-1500 demonstrated a mean half-life of 37.8 and 33.8 days for 10 and 30 mg\/kg, respectively, supportive of monthly dosing; dose-proportional exposure was suggested over the 3 to 30 mg\/kg range. TNX-1500 blocked the primary T cell-dependent antibody response to keyhole limpet hemocyanin (KLH) at all doses and blocked the secondary response at the 10 and 30 mg\/kg doses. At 3 mg\/kg, TNX-1500 reduced peak secondary response to KLH by ~ 70% relative to placebo. TNX-1500 administration was associated with immediate and sustained reduction in soluble CD154. Overall, TNX-1500 demonstrated a safety profile and pharmacologic properties that support further development as an agent with potential for prevention of organ transplant rejection and treatment for autoimmune conditions.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42053701\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20260429124700&amp;v=2.19.0.post6+133c1fe\">42053701<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-026-02028-8\">10.1007\/s10875-026-02028-8<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2026 Apr 29. doi: 10.1007\/s10875-026-02028-8. Online ahead of print. ABSTRACT Blocking CD154 (CD40L) has the potential to prolong transplanted solid organ graft survival and treat autoimmune diseases. However, first-generation anti-CD154 IgG1 monoclonal antibodies (mAbs) were associated with an increased risk of thrombosis linked to Fc binding to Fc\u03b3RIIa (CD32A). Here, we describe &#8230; <a title=\"First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/first-in-human-phase-1-randomized-double-blind-placebo-controlled-study-of-tnx-1500-an-fc-modified-anti-cd154-monoclonal-antibody-evaluating-the-safety-tolerability-pharmacokinetics-and-pharm\/\" aria-label=\"Read more about First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-62937","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62937","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=62937"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62937\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=62937"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=62937"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=62937"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}