Radicava/edaravone findings in biomarkers from ALS (REFINE ALS): Protocol and study design

Abstract (245/250 words) Objectives: Identify putative biomarkers that may serve as quantifiable, biological, nonclinical measures of the pharmacodynamic effect of edaravone in ALS. Real-world treatment outcomes will also be reported. Methods: This is a prospective, observational, longitudinal, multicenter (up to 40 sites) US study (Clinicaltrials.gov; NCT04259255) with at least 200 ALS patients who will receive edaravone for 24 weeks (6 cycles; FDA-approved regimen). All participants must either be treatment-naive for edaravone or be more than 1 month without receiving any edaravone dose prior to screening. Biomarker quantification and other assessments will be performed at baseline (prior to cycle 1) and during cycles 1, 3, and 6. Selected biomarkers of oxidative stress, inflammation, neuronal injury and death, and muscle injury, as well as biomarker discovery panels (EpiSwitchTM and SOMAscan®), will be evaluated and, when feasible, compared with biobanked samples. Clinical efficacy assessments will include the ALS Functional Rating Scale-Revised, King’s clinical staging, ALS Assessment Questionnaire, Appel ALS Score (Rating Scale), slow vital capacity, hand-held dynamometry and grip strength, and time to specified states of disease progression or death. DNA samples will also be collected for potential genomic evaluation. The predicted rate of progression and survival, and their potential correlations with biomarkers, will be evaluated. Adverse events related to the study will be reported. Results: The study is estimated to be completed in 2022 with an interim analysis planned. Conclusion: Findings may help to further understanding of the pharmacodynamic effect of edaravone, including changes in biomarkers, in response to treatment.