Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)

NCT04259255 | Unknown FDA Drug

• 1 other identifier: REFINE-ALS
• Study Type: observational
• Target: 300
• Locations: 2 countries
• Sites: 20

Brief Summary

REFINE-ALS is a prospective, observational, longitudinal, multicenter study designed to identify biomarkers to serve as quantifiable biological non-clinical measures of Edaravone effects in ALS. Epigenetic and protein biomarkers will also be investigated.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Keywords

biomarkers; edaravone; Radicava®; Radicava ORS®; motor neuron disease

Outcome Measures

Primary Outcomes (8)

• Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for 8-F2 isoprostanes.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of 3-nitrotyrosine (3-NT) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for 3-NT.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples 8-OHdG.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of urate as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for urate.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of matrix metalloproteinase-9 (MMP-9) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for MMP-9.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of urinary neutrophin receptor p75 as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for urinary neutrophin receptor p75.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of neurofilaments (Nf) (Heavy and Light) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for neurofilaments (Nf) (Heavy and Light).

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change in levels of creatinine as a potential biomarkers of oxidative stress, inflammation or neurodegeneration.

  Collection of blood and/or urine samples for creatinine.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Secondary Outcomes (6)

• Change from baseline in the ALSFRS-R (ALS Functional Rating Scale .Revised) Score

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change from baseline in the King's Clinical Staging.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change from baseline in the ALSAQ-40 (ALS Assessment Questionnaire).

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change from baseline in the Appel ALS Score.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

• Change from baseline in slow vital capacity.

  Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Study Arms (1)

Edaravone (Radicava®/Radicava ORS®)

During an estimated 12-month period, eligible participants who are prescribed Edaravone within the approved indication will be invited to participate in the study.

Drug: Edaravone (Radicava®/Radicava ORS®)

Interventions

Edaravone (Radicava®/Radicava ORS®) DRUG

Participants will be followed from enrollment up to 24 weeks after treatment initiation (6 treatment cycles - 28 days per cycle, corresponding to a treatment period of approximately 24 weeks) or premature study discontinuation. Biomarker testing and clinical assessments will be performed at baseline (at enrollment or before the start of cycle 1), and at cycles 1, 3, and 6. Dosing is 60 mg daily by intravenous infusion for 14 days for the initial treatment cycle, followed by daily dosing on 10 out of 14 days in subsequent treatment cycles.

Also known as: Radicava®, Radicava ORS®

Edaravone (Radicava®/Radicava ORS®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted in participants who have sporadic or familial amyotrophic lateral sclerosis (ALS) as defined by revised El Escorial criteria. Participants must provide written informed consent prior to screening. At screening, eligible patient must be at least 18 years old with a decision made to prescribe Edaravone prior to consenting. Participants who are either Edaravone naïve or who did not receive any Edaravone dose within one month of consenting are eligible for inclusion given they meet all other protocol requirements.

You may qualify if:

• Male and female aged 18 years or older at enrollment
• Sporadic or familial ALS diagnosed as possible, probable, probable-laboratory supported or definite as defined by the World Federation of Neurology revised El Escorial criteria
• Decision made to prescribe Edaravone prior to screening
• Participant will likely be able to obtain commercial Edaravone and likely to complete 6 cycles of treatment, per site investigator estimation
• Participant either naïve to Edaravone or who did not receive any Edaravone does within 1 month prior to screening
• Signed informed consent by the subject, or a witness if a subject cannot read or write or is physically unable to talk or write, obtained before any study-related activities are undertaken

You may not qualify if:

• Participant with a contraindication to Edaravone
• Participant is participating in an interventional clinical trial

Sponsors & Collaborators

• Tanabe Pharma America, Inc.: lead
• Massachusetts General Hospital: collaborator

Study Sites (20)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

UCLA Als Clinic

Los Angeles, California, 90024, United States

Location

UC Davis Health

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94417, United States

Location

University of Colorado

Denver, Colorado, 80309, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida, Jacksonville -Neurology Research Department

Jacksonville, Florida, 32209, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Mercy Health

Grand Rapids, Michigan, 49503, United States

Location

Neurology Associates, P.C.

Lincoln, Nebraska, 68506, United States

Location

Las Vegas Clinic

Las Vegas, Nevada, 89145, United States

Location

OhioHealth

Columbus, Ohio, 43215, United States

Location

Jefferson Weinberg ALS Center

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Lewis Katz School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

SunnyBrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

• Berry J, Brooks B, Genge A, Heiman-Patterson T, Appel S, Benatar M, Bowser R, Cudkowicz M, Gooch C, Shefner J, Westra J, Agnese W, Merrill C, Nelson S, Apple S. Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design. Neurol Clin Pract. 2021 Aug;11(4):e472-e479. doi: 10.1212/CPJ.0000000000000968.

  PMID: 34476128 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Edaravone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antipyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• James Berry, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: February 6, 2020
• Study Start: October 21, 2019
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (19)