{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:03:57Z","timestamp":1787965437659,"version":"build-2784847793"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"AM-Pharma"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypophosphatasia is a rare genetic disease caused by deficient alkaline phosphatase (AP) activity. In adults, this causes functional limitations, substantial disability with pain and reduced quality of life. This Phase 1b, single-center, open-label trial investigated ilofotase alfa, a fully human recombinant protein intended as enzyme replacement therapy, in adults with hypophosphatasia. Changes in plasma levels of AP substrates inorganic pyrophosphate and pyridoxal-5\u2032-phosphate were evaluated. Participants were randomized 1:1 to receive at 0.8 or 3.2\u00a0mg\/kg ilofotase alfa intravenously over 1\u00a0h. Twelve participants were enrolled and completed the trial. At baseline, all participants had reduced AP activity and elevated pyridoxal-5\u2032-phosphate. The greatest reduction in inorganic pyrophosphate and pyridoxal-5\u2032-phosphate occurred 2\u00a0h after start of dosing in both treatment groups. Across the 10-d follow-up period, inorganic pyrophosphate values returned to baseline levels more rapidly in the 0.8\u00a0mg\/kg group compared with the 3.2\u00a0mg\/kg group. Mean circulating AP activity peaked 24\u00a0h after dosing and subsequently declined but remained above the lower limit of normal throughout the study. A dose-proportional increase in ilofotase alfa was observed, reaching peak concentration 1-h post-infusion. Eight treatment-emergent adverse events occurred, all classified as mild. These data demonstrate that single-dose ilofotase alfa enhances AP activity and results in dose-dependent reductions in primary disease-specific biomarkers without undesired effects on mineral homeostasis.<\/jats:p>\n                  <jats:p>Clinical trial registration number: ClinicalTrials.gov number: NCT05890794.<\/jats:p>","DOI":"10.1093\/jbmr\/zjaf185","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:57:10Z","timestamp":1765025830000},"page":"231-241","source":"Crossref","is-referenced-by-count":2,"title":["A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-3388","authenticated-orcid":false,"given":"Lothar","family":"Seefried","sequence":"first","affiliation":[{"name":"Osteology\/Clinical Trial Unit, University of Wuerzburg , 97074 Wuerzburg 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