TY - JOUR
T1 - Effect of RNS60 in amyotrophic lateral sclerosis
T2 - a phase II multicentre, randomized, double-blind, placebo-controlled trial
AU - RNS60-ALS Study Group
AU - Beghi, Ettore
AU - Pupillo, Elisabetta
AU - Bianchi, Elisa
AU - Bonetto, Valentina
AU - Luotti, Silvia
AU - Pasetto, Laura
AU - Bendotti, Caterina
AU - Tortarolo, Massimo
AU - Sironi, Francesca
AU - Camporeale, Laura
AU - Sherman, Alexander V
AU - Paganoni, Sabrina
AU - Scognamiglio, Ada
AU - De Marchi, Fabiola
AU - Bongioanni, Paolo
AU - Del Carratore, Renata
AU - Caponnetto, Claudia
AU - Diamanti, Luca
AU - Martinelli, Daniele
AU - Calvo, Andrea
AU - Filosto, Massimiliano
AU - Padovani, Alessandro
AU - Piccinelli, Stefano Cotti
AU - Ricci, Claudia
AU - Dalla Giacoma, Stefania
AU - De Angelis, Nicoletta
AU - Inghilleri, Maurizio
AU - Spataro, Rossella
AU - La Bella, Vincenzo
AU - Logroscino, Giancarlo
AU - Lunetta, Christian
AU - Tarlarini, Claudia
AU - Mandrioli, Jessica
AU - Martinelli, Ilaria
AU - Simonini, Cecilia
AU - Zucchi, Elisabetta
AU - Monsurrò, Maria Rosaria
AU - Ricciardi, Dario
AU - Trojsi, Francesca
AU - Riva, Nilo
AU - Filippi, Massimo
AU - Simone, Isabella Laura
AU - Sorarù, Gianni
AU - Spera, Cristina
AU - Florio, Lucia
AU - Messina, Sonia
AU - Russo, Massimo
AU - Siciliano, Gabriele
AU - Conte, Amelia
AU - Saddi, Maria Valeria
N1 - © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Humans
KW - Amyotrophic Lateral Sclerosis/diagnosis
KW - Quality of Life
KW - Neurodegenerative Diseases
KW - Double-Blind Method
KW - Biomarkers
KW - Treatment Outcome
U2 - 10.1111/ene.15573
DO - 10.1111/ene.15573
M3 - Article
C2 - 36148821
SN - 1351-5101
VL - 30
SP - 69
EP - 86
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 1
ER -