Long-term survival of participants in a phase II randomized trial of RNS60 in amyotrophic lateral sclerosis

• Published in: Brain, behavior, and immunity behavior, and immunity, 2024-11, Vol.122, p.456-462
• Main Authors: Pupillo, Elisabetta, Bianchi, Elisa, Bonetto, Valentina, Pasetto, Laura, Bendotti, Caterina, Paganoni, Sabrina, Mandrioli, Jessica, Mazzini, Letizia
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Clinical trial; Forced vital capacity; Survival
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2024.08.044

•This study providesevidence of a possible positive effect of RNS60 on ALS outcomes.•Median survival was 6 months longer in people randomized to RNS60 compared to placebo.•Association of rate of respiratory decline with survival was evaluated.•RNS60 group experienced slower rates of respiratory decline.•The rate of respiratory decline was inversely associated with long-term survival. Positive effects of RNS60 on respiratory and bulbar function were observed in a phase 2 randomized, placebo-controlled trial in people with amyotrophic lateral sclerosis (ALS). Objective: to investigate the long-term survival of trial participants and its association with respiratory status and biomarkers of neurodegeneration and inflammation. A randomized, double blind, phase 2 clinical trial was conducted. Trial participants were enrolled at 22 Italian Expert ALS Centres from May 2017 to January 2020. Vital status of all participants was ascertained thirty-three months after the trial’s last patient last visit (LPLV). Participants were patients with Amyotrophic Lateral Sclerosis, classified as slow or fast progressors based on forced vital capacity (FVC) slope during trial treatment. Demographic, clinical, and biomarker levels and their association with survival were also evaluated. Mean duration of follow-up was 2.8 years. Long-term median survival was six months longer in the RNS60 group (p = 0.0519). Baseline FVC, and rates of FVC decline during the first 4 weeks of trial participation, were balanced between the active and placebo treatment arms. After 6 months of randomized, placebo-controlled treatment, FVC decline was significantly slower in the RNS60 group compared to the placebo group. Rates of FVC progression during the treatment were strongly associated with long-term survival (median survival: 3.7 years in slow FVC progressors; 1.6 years in fast FVC progressors). The effect of RNS60 in prolonging long-term survival was higher in participants with low neurofilament light chain (NfL) (median survival: >4 years in low NfL − RNS60 group; 3.3 years in low NfL − placebo group; 1.9 years in high NfL − RNS60 group; 1.8 years in high NfL − placebo group) and Monocyte Chemoattractant Protein-1 (MCP-1) (median survival: 3.7 years in low MCP-1 − RNS60 group; 2.3 years in low MCP-1 − placebo group; 2.8 years in high MCP-1 − RNS60 group; 2.6 years in high MCP-1 − placebo group) levels at baseline. In this post-hoc analysis, long term survival was longer in participants randomiz