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

James Berry, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Benjamin Brooks, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Angela Genge, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Terry Heiman-Patterson, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Stanley Appel, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Michael Benatar, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Robert Bowser, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.Follow
Merit Cudkowicz, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Clifton Gooch, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Jeremy Shefner, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.Follow
Jurjen Westra, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Wendy Agnese, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Charlotte Merrill, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Sally Nelson, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Stephen Apple, Massachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.

Document Type

Article

Abstract

Objectives: To 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. Methods: This 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. Results: The study is estimated to be completed in 2022 with an interim analysis planned. Conclusions: Findings may help to further the understanding of the pharmacodynamic effect of edaravone, including changes in biomarkers, in response to treatment.

Publication Date

9-4-2021

Publication Title

Neurology. Clinical practice

ISSN

2163-0402

Volume

11

Issue

4

First Page

e472

Last Page

e479

PubMed ID

34476128

Digital Object Identifier (DOI)

10.1212/CPJ.0000000000000968

This document is currently not available here.

Share

COinS