2026 ECNP Congress

PS02-2113

Efficacy and safety of NH102 in major depressive disorder: a randomised, phase 2 proof-of-concept clinical trial

Shen He — W. Zhiqiang, C. Jingxu, G. Jianliang, L. Zhifen, Y. Xueqin, Y. Yuanjian, L. Tao, T. Zhonglin, L. Dongmei, Z. Futao, X. Yongming, Z. Rong, Z. Yunshao, L. Xuan, W. Feiyan, Q. Mincai, Z. Bo, Q. Yan, L. Yansong, X. Zhiyuan, Y. Dong, S. Xiuli, Y. Yimin, L. Huafang · ShangHai Mental Health Center, Department of Psychiatry, ShangHai, China

2026 ECNP Congress

Background

Major depressive disorder (MDD) is frequently associated with inadequate response to antidepressant treatment, poor tolerability overall. Despite the availability of multiple pharmacological options, a substantial proportion of patients still fail to achieve remission with first‑line therapies, highlighting the need for novel agents with improved efficacy and tolerability profiles. NH102 is a novel multimodal antidepressant combining potent serotonin–norepinephrine reuptake inhibition with moderate 5‑HT₂A antagonism. This pharmacological profile may offer both robust antidepressant effects and potential advantages in safety and tolerability. This study therefore evaluated its efficacy and safety in adults with MDD patients.

Methods

In this multicenter, randomized, double‑blind, placebo‑controlled, phase 2 proof of concept trial with duloxetine as an active control, 243 adult patients with DSM‑5 MDD were randomized in a 1:1:1:1:1 ratio to NH102 30 mg, 20 mg, or 10 mg, placebo, or duloxetine 60 mg for 6 weeks. The primary endpoint was the change from baseline in the 17‑item Hamilton Depression Rating Scale (HAMD‑17) total score at week 6, analyzed with a mixed‑effects model for repeated measures (MMRM), adjusting for baseline score, visit, episode type, and treatment‑by‑visit interaction. The key secondary endpoint was change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score. Additional secondary outcomes included Clinical Global Impression – Severity (CGI‑S) and Clinical Global Impression – Improvement (CGI‑I), as well as several other prespecified secondary measures.

Results

At week 6, NH102 30 mg showed a greater improvement in HAMD‑17 score compared with placebo (least‑squares mean [LSM] difference, −2.8; 95% CI, −5.4 to −0.2; P = 0.036). The reduction in HAMD‑17 score with NH102 30 mg was numerically greater than that observed with duloxetine 60 mg (LSM difference, −0.3; 95% CI, −2.9 to 2.2; P = 0.7913); however, the between‑group difference did not reach statistical significance. NH102 10 mg and 20 mg showed numerically greater reductions in HAMD‑17 score than placebo, with differences that were not statistically significant.

Consistent with the primary endpoint, NH102 30 mg also significantly improved the key secondary endpoint, MADRS score, compared with placebo (P = 0.0045). For other secondary outcomes, NH102 30 mg showed greater improvements in CGI‑I (P=0.004) and CGI‑S(P=0.008) scores. Across all three dose groups, NH102 was well tolerated, with most treatment‑emergent adverse events being mild to moderate in severity. Compared with duloxetine, NH102 was associated with a numerically lower incidence of gastrointestinal treatment‑emergent adverse events, including nausea and diarrhea.

Conclusions

NH102 30 mg showedpreliminary efficacy on the primary depressive symptom outcome and exhibited an acceptable tolerability profile in adults with MDD. Its combined serotonin–norepinephrine reuptake inhibition with moderate 5‑HT₂A antagonism supports further clinical development of NH102 as a mechanistically novel antidepressant candidate.Larger and longer‑term studies are needed to confirm these findings and further characterize its overall benefit–risk profile profile.

References

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