Huoling Shengji granule in amyotrophic lateral sclerosis: A multicenter, randomized, double-blind,...

Currently, no curative therapies exist for Amyotrophic Lateral Sclerosis (ALS). This study aimed to evaluate the efficacy and safety of Huoling Shengji granules (HLSJ), a traditional Chinese medicine (TCM), compared to the standard treatment riluzole. A multicenter, randomized, double-blind, double-dummy, active-controlled Phase II clinical trial was conducted across 11 centers in China. A total of 140 ALS patients were randomly assigned (1:1) to receive either HLSJ or riluzole for 48 weeks. The primary endpoint, analyzed in the full analysis set (FAS), was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Week 48. Safety profiles were comparable between groups, with no significant difference in adverse events (80.28% vs. 80.56%, P = 0.9671). Analysis using the pre-specified Last Observation Carried Forward (LOCF) method showed a numerical advantage for HLSJ (1.07 points) but lacked statistical superiority. However, a more scientific analysis using the Mixed Model for Repeated Measures (MMRM), recommended for progressive diseases, indicated that HLSJ was significantly superior to riluzole in slowing ALSFRS-R score decline (Least Squares Mean Difference [LSMD]: 2.29 points; 95% confidence interval [CI]: 0.52 to 4.06; P = 0.0114). While the LOCF model showed no statistical difference, the MMRM analysis confirmed that HLSJ demonstrated significant efficacy superior to riluzole with a favorable safety profile. These findings provide a critical basis for conducting pivotal Phase III confirmatory trials of HLSJ for ALS treatment.