Amyotrophic Lateral SclerosisNCT04259255

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

An observational study of Amyotrophic Lateral Sclerosis and ALS, run by Shionogi at 20 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Amyotrophic Lateral Sclerosis, ALS
What is being tested?: Edaravone (Radicava®/Radicava ORS®)
Type of treatment: Injection or infusion
How many people: 74 participants
Where: 20 sitesin 2 countries
Study dates: 21 Oct 2019to 24 Nov 2024
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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.

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

20 sites in 2 countries.

Country

City, postcode or hospital

20 sites in 2 countries

United States19 sites

Johns Hopkins University
Baltimore, Maryland, 21205
Massachusetts General Hospital
Boston, Massachusetts, 02214
OhioHealth
Columbus, Ohio, 43215
University of Colorado
Denver, Colorado, 80309
Mercy Health
Grand Rapids, Michigan, 49503
University of Florida, Jacksonville -Neurology Research Department
Jacksonville, Florida, 32209
Mayo Clinic Florida
Jacksonville, Florida, 32224
Las Vegas Clinic
Las Vegas, Nevada, 89145
Neurology Associates, P.C.
Lincoln, Nebraska, 68506
UCLA Als Clinic
Los Angeles, California, 90024
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Jefferson Weinberg ALS Center
Philadelphia, Pennsylvania, 19107
Temple University Lewis Katz School of Medicine
Philadelphia, Pennsylvania, 19140
Barrow Neurological Institute
Phoenix, Arizona, 85013
UC Davis Health
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84112
University of California, San Francisco
San Francisco, California, 94417
University of South Florida
Tampa, Florida, 33612
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007

Other trials in United States

Canada1 site

SunnyBrook Research Institute
Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Read the detailed description

Treatment will be prescribed by HCPs in accordance with their clinical judgement and the prescribing information for Edaravone. The decision to prescribe Edaravone to the participants should be made separately from the decision to enroll then in the study. There will be no randomized assignments to treatment and no restrictions on the use of commercially available medications (but those participating in an experimental study, even if taking Edaravone, will be excluded). No experimental treatment is evaluated in this study. The intervention is limited to the collection of blood and urine samples for biomarker testing.

During the estimated study period, eligible patients who are prescribed Edaravone within the approved indication will be invited to participate in the study. An initial screening/baseline visit will be scheduled for participants who are considered for study participation.

Participants in this study will be followed from enrollment up to 24 weeks after treatment initiation (6 treatment cycles [each cycle consisting of 28 days], corresponding to a treatment period of approximately 24 weeks) or premature study discontinuation. Throughout the study period, the investigators will record participant baseline and follow-up information and perform clinical and biomarker assessments.

Conditions: Amyotrophic Lateral Sclerosis, ALS
Being tested: Edaravone (Radicava®/Radicava ORS®)
Keywords: biomarkers, edaravone, Radicava®, Radicava ORS®, motor neuron disease
Medical subject headings: Amyotrophic Lateral Sclerosis, Motor Neuron Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Edaravone (Radicava®/Radicava ORS®)Drug
Also called Radicava®, Radicava ORS®
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.

Study groups in NCT04259255
Study group	Role	What they receive
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. Receives: Drug: Edaravone (Radicava®/Radicava ORS®)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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
The ALSFRS-R is a quickly administered ordinal rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the King's Clinical Staging.
The King's clinical staging is based on the number of body regions affected by ALS and the presence of respiratory or nutritional failure.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the ALSAQ-40 (ALS Assessment Questionnaire).
The ALSAQ-40 is a questionnaire that consists of 40 questions/items with 5 discrete scales: physical mobility, activities of daily living and independence, eating and drinking, communication, emotional reactions.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the Appel ALS Score.
The Appel ALS score consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in slow vital capacity.
The vital capacity (VC) (percent of predicted normal) will be determined, using the upright slow VC method.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in hand-held dynamometry.
Hand-held dynamometry (HHD) will be used as a quantitative measure of muscle strength for this study.
Measured: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Oct 201924 Nov 2024

First posted6 Feb 2020
Study start21 Oct 2019
Primary completion24 Nov 2023
Study completion24 Nov 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
More trials run by ShionogiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Other
Time perspective: Prospective
Enrolment: 74 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04259255
Sponsor's protocol ID: REFINE-ALS
Status last verified: Jun 2026
First submitted: 27 Jan 2020
Last updated: 30 Jun 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 34476128

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Amyotrophic Lateral Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
ClinicalTrials.gov ID: NCT04259255
Acronym / sponsor ID: REFINE-ALS
Conditions: Amyotrophic Lateral Sclerosis, ALS
Keywords: biomarkers, edaravone, Radicava®, Radicava ORS®, motor neuron disease
Study type: Observational
Recruitment status: Completed
Enrolment: 74 participants (actual)
Lead sponsor: ShionogiIndustry (pharma, biotech, devices)
Study start: 21 Oct 2019 (actual)
Primary completion: 24 Nov 2023 (actual)
Study completion: 24 Nov 2024 (actual)
First posted: 6 Feb 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Other
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Edaravone (Radicava®/Radicava ORS®)	–	Drug: 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
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.

Key inclusion criteria (6 listed)

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

Key exclusion criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Edaravone (Radicava®/Radicava ORS®)Also: Radicava®, Radicava ORS®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.	Drug	Edaravone (Radicava®/Radicava ORS®)

Primary outcome

Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for 8-F2 isoprostanes.
Change in levels of 3-nitrotyrosine (3-NT) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for 3-NT.
Change in levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples 8-OHdG.
Change in levels of urate as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for urate.
Change in levels of matrix metalloproteinase-9 (MMP-9) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for MMP-9.
Change in levels of urinary neutrophin receptor p75 as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for urinary neutrophin receptor p75.
Change in levels of neurofilaments (Nf) (Heavy and Light) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for neurofilaments (Nf) (Heavy and Light).
Change in levels of creatinine as a potential biomarkers of oxidative stress, inflammation or neurodegeneration.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Collection of blood and/or urine samples for creatinine.

6 secondary outcomes

Change from baseline in the ALSFRS-R (ALS Functional Rating Scale .Revised) Score
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the King's Clinical Staging.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the ALSAQ-40 (ALS Assessment Questionnaire).
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in the Appel ALS Score.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in slow vital capacity.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Change from baseline in hand-held dynamometry.
Time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
Derived from this study: PubMed 34476128Berry 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Berry, MD, MPH principal investigator

Massachusetts General Hospital

20 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Amyotrophic Lateral Sclerosis and ALS, run by Shionogi at 20 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration. (time frame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04259255, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.