2026 ECNP Congress

PS01-1227

HS-10380 in patients with schizophrenia: a phase 2b randomised placebo– and active-controlled trial

Huafang Li — G. Li, Z. Fang, Z. Wang, Y. Zhang, J. Jia, S. Chen, H. Chen, Y. Wang, G. Zhao, Y. Meng, Y. Li, M. Qian, L. Song, J. Zhai, Y. Zhang, X. Liu, Y. Tian, C. Chen, L. Yu, X. Zhang · Shanghai Mental Health Center- Shanghai Jiao Tong University School of Medicine, Psychiatry, Shanghai, China

2026 ECNP Congress

Introduction

Unmet need persists for novel schizophrenia therapeutics offering improved efficacy and mitigated safety concerns. HS-10380 is an oral multi-target agent acting on dopamine and serotonin pathways, designed to address both positive and negative symptoms of schizophrenia. Previous studies (NCT05480592, NCT05964790) suggest promising efficacy signals with a favorable safety profile.

Aims

:To evaluate the efficacy, safety, and pharmacokinetics (PK) of HS-10380 in patients with acute schizophrenia (NCT07550387).

Methods

This phase 2b, randomized, double-blind, placebo- and active-controlled trial was conducted across 24 centers in China. Eligible participants met DSM-5 criteria for schizophrenia with a positive and negative syndrome scale (PANSS) total score of 80-120, and were in the acute phase with hospitalization for the current exacerbation within 2 weeks prior to screening. Participants were randomized 2:2:2:1:2 to receive a fixed-flexible dosing regimen of once-daily oral HS-10380 (1.5–3 mg, 4.5–6 mg, or 6–9 mg), aripiprazole (10–20 mg), or placebo each morning for 42 days, followed by a 1-week taper period. The primary efficacy endpoint was the change from baseline in PANSS total score on Day 42, analyzed in all randomized patients who received at least one dose of study drug and had both baseline and at least one post-baseline PANSS assessment (full analysis set [FAS]).

Results

A total of 363 Chinese participants were randomized to HS-10380 1.5–3 mg (n=81), HS-10380 4.5–6 mg (n=80), HS-10380 6–9 mg (n=81), aripiprazole (n=40), or placebo (n=81). The primary endpoint was met. Based on FAS (n=359), the least squares mean differences (LSMD) in PANSS total score change from baseline on Day 42 versus placebo were: -16.7 (95% CI: -22.5, -10.9; P<0.0001) for HS-10380 1.5–3 mg, -13.2 (95% CI: -18.9, -7.4; P<0.0001) for HS-10380 4.5–6 mg, -14.7 (95% CI: -20.5, -8.8; P<0.0001) for HS-10380 6–9 mg, and -12.1 (95% CI: -19.1, -5.1; P=0.0007) for aripiprazole. Furthermore, on Day 42, HS-10380 demonstrated significantly greater improvements versus placebo in PANSS negative subscale (LSMD vs. placebo: -4.4 to -3.1 across dose groups), in Marder’s negative factor (LSMD: -4.5 to -2.9) and in cognitive factor (LSMD: -3.6 to -3.2), as well as in PANSS positive, general psychopathology subscales and response rate. Notably, HS‑10380 showed numerically superior efficacy trends compared to aripiprazole across these endpoints. Among HS-10380-treated patients (n=242), common treatment-related adverse events (TRAEs) included: extrapyramidal disorder, constipation, nausea, vomiting, akathisia, hyperprolactinemia, dizziness, and insomnia. All extrapyramidal disorder events were mild to moderate in severity, and none led to dose interruption or study discontinuation. For PK analyses, the exposure of HS-10380 increased with increasing dose and was at steady state on Day 42.

Conclusions

In Chinese adults with acute schizophrenia, HS-10380 demonstrated significant efficacy, with particularly robust improvements in PANSS negative and cognitive symptoms, a key unmet need in antipsychotics. The safety profile was favorable with no new safety concerns identified. These results support further clinical development of HS-10380.

References

No references