Safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of MG-ZG122, a long-acting humanized anti-thymic stromal lymphopoietin mAb, in healthy Chinese: a randomized, double-blind, placebo-controlled, dose-escalation, phase I study.

Abstract

Background: This phase I study aimed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of MG-ZG122, an anti-thymic stromal lymphopoietin mAb, in a healthy Chinese population.

Methods: A randomized, double-blind, placebo-controlled, and dose-escalation design was used. Four dose cohorts (52.5, 105, 210, and 420 mg) with 10 participants each were randomized to receive subcutaneously (SC) a single dose of MG-ZG122 or placebo (8:2), except for the 52.5 mg with 4 participants (2:2).

Results: Among participants who received MG-ZG122 (n = 26/34), most treatment-emergent adverse events (TEAEs) were grade 1 or 2. A single dose of MG-ZG122 exhibited a dose-dependent increase in the serum concentration ranging from 52.5 to 420 mg. It showed a half-life of up to 80 days and is intended to support a once-every-6-month administration. Dose-dependent reductions in peripheral blood eosinophil counts were observed in the 210 and 420 mg dose cohorts, with a greater decrease at the 420 mg and a sustained response through day 211.

Conclusions: MG-ZG122 was safe and well-tolerated with favorable PK profiles after a single SC injection in healthy Chinese at doses ranging from 52.5 to 420 mg, providing preliminary evidence for further evaluation.

Clinical trial registration: This study was registered with ClinicalTrials.gov, NCT05659927.