Authors
Sufeng Zhou, Xiufen Zhu, Yuchen Sheng, Lu Wang, Feng Shao, Hua Lin
Published in
Expert opinion on investigational drugs. Sep 16, 2026. Epub Sep 16, 2026.
Abstract
TST002 is a humanized IgG4 monoclonal antibody targeting sclerostin for osteoporosis treatment. This first-in-human study investigated its safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) after intravenous infusion in Chinese men and postmenopausal women with low bone mineral density (BMD).
In a randomized, double-blind, placebo-controlled, dose-escalation trial, 32 subjects were assigned to four dose cohorts (3:1 ratio to receive single TST002 doses of 200, 400, 800, or 1200 mg or placebo) with 85 days of follow-up. PK, PD, safety, and immunogenicity were assessed. An exploratory population PK-PD model incorporating target-mediated drug disposition (TMDD) was developed.
Among TST002 recipients (n = 24), most treatment-related adverse events were grade 1 in severity. Nonlinear PK was observed, with greater-than-dose-proportional exposure and a mean half-life of 4.38-8.06 days. Increases in serum sclerostin and lumbar spine BMD, and decreases in β-CTX were observed. An exploratory population TMDD-PD model was developed to describe the observed time courses of TST002, sclerostin, and β-CTX within the present phase I dataset.
TST002 was well tolerated and showed preliminary PD activity. Exploratory TMDD-based PK/PD modeling provided preliminary insights into exposure-response relationships, limited by the sample size, single-dose design, and unavailable bone formation marker assessment.
This study was registered at Clinicaltrials.gov (NCT05391776).
PMID:
42747328
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.
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