Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design

James Berry, Benjamin Brooks, Angela Genge, Terry Heiman-Patterson, Stanley Appel, Michael Benatar, Robert Bowser, Merit Cudkowicz, Clifton Gooch, Jeremy Shefner, Jurjen Westra, Wendy Agnese, Charlotte Merrill, Sally Nelson, Stephen Apple

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


ObjectivesTo identify putative biomarkers that may serve as quantifiable, biological, nonclinical measures of the pharmacodynamic effect of edaravone in amyotrophic lateral sclerosis (ALS) and to report real-world treatment outcomes.MethodsThis is a prospective, observational, longitudinal, multicenter (up to 40 sites) US study (Clinicaltrials.gov; NCT04259255) with at least 200 patients with ALS who will receive edaravone for 24 weeks (6 cycles; Food and Drug Administration-approved regimen). All participants must either be treatment naive for edaravone or be more than 1 month without receiving any edaravone dose before screening. Biomarker quantification and other assessments will be performed at baseline (before 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 (EpiSwitch 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-40, 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 rates of progression and survival, and their potential correlations with biomarkers, will be evaluated. Adverse events related to the study will be reported.ResultsThe study is estimated to be completed in 2022 with an interim analysis planned.ConclusionsFindings may help to further the understanding of the pharmacodynamic effect of edaravone, including changes in biomarkers, in response to treatment.

Original languageEnglish (US)
Pages (from-to)E472-E479
JournalNeurology: Clinical Practice
Issue number4
StatePublished - Aug 1 2021

ASJC Scopus subject areas

  • Clinical Neurology


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