Effect of <scp>RNS60</scp> in amyotrophic lateral sclerosis: a phase <scp>II</scp> multicentre, randomized, double‐blind, placebo‐controlled trial
Ettore Beghi, Elisabetta Pupillo, Elisa Bianchi, Valentina Bonetto, Silvia Luotti, Laura Pasetto, Caterina Bendotti, Massimo Tortarolo, Francesca Sironi, Laura Camporeale, Alexander Sherman, Sabrina Paganoni, Ada Scognamiglio, Fabiola De Marchi, Paolo Bongioanni, R. Del Carratore, Claudia Caponnetto, Luca Diamanti, Daniele Martinelli, Andrea Calvo, Massimiliano Filosto, Alessandro Padovani, Stefano Cotti Piccinelli, Claudia Ricci, Stefania Dalla Giacoma, Nicoletta De Angelis, Maurizio Inghilleri, Rossella Spataro, Vincenzo La Bella, Giancarlo Logroscino, Christian Lunetta, Claudia Tarlarini, Jessica Mandrioli, Ilaria Martinelli, Cecilia Simonini, Elisabetta Zucchi, Maria Rosaria Monsurrò, Dario Ricciardi, Francesca Trojsi, Nilo Riva, Massimo Filippi, Isabella Laura Simone, Gianni Sorarú, Cristina Spera, Lucía Florio, Sonia Messina, Massimo Russo, Gabriele Siciliano, Amelia Conte, Maria Valeria Saddi, Nicola Carboni, Letizia Mazzini, the RNS60‐ALS Study Group
Abstract
BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. METHODS: This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. RESULTS: Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. CONCLUSIONS: The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation.