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

August 23, 2023 updated by: Mitsubishi Tanabe Pharma America Inc.
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.

Study Overview

Status

Active, not recruiting

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.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
    • California
      • Los Angeles, California, United States, 90024
        • UCLA Als Clinic
      • Sacramento, California, United States, 95817
        • UC Davis Health
      • San Francisco, California, United States, 94417
        • University of California, San Francisco
    • Colorado
      • Denver, Colorado, United States, 80309
        • University of Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida, Jacksonville -Neurology Research Department
      • Tampa, Florida, United States, 33612
        • University of South Florida
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02214
        • Massachusetts General Hospital
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Neurology Associates, P.C.
    • Nevada
      • Las Vegas, Nevada, United States, 89145
        • Las Vegas Clinic
    • Ohio
      • Columbus, Ohio, United States, 43215
        • OhioHealth
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Lewis Katz School of Medicine
      • Philadelphia, Pennsylvania, United States, 19107
        • Jefferson Weinberg ALS Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

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.

Other Names:
  • Radicava®
  • Radicava ORS®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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.
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).
The King's clinical staging is based on the number of body regions affected by ALS and the presence of respiratory or nutritional failure.
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).
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.
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).
The Appel ALS score consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function.
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).
The vital capacity (VC) (percent of predicted normal) will be determined, using the upright slow VC method.
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).
Hand-held dynamometry (HHD) will be used as a quantitative measure of muscle strength for this study.
Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: James Berry, MD, MPH, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 21, 2019

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

January 27, 2020

First Submitted That Met QC Criteria

February 4, 2020

First Posted (Actual)

February 6, 2020

Study Record Updates

Last Update Posted (Actual)

August 24, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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