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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04259255
• Other study ID #: REFINE-ALS
• Status: Active, not recruiting
• Start date: October 21, 2019
• Est. completion date: March 2024

Study information

• Verified date: August 2023
• Source: Mitsubishi Tanabe Pharma America Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• Edaravone (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.

Locations

Country	Name	City	State
Canada	SunnyBrook Research Institute	Toronto	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	OhioHealth	Columbus	Ohio
United States	University of Colorado	Denver	Colorado
United States	Mercy Health	Grand Rapids	Michigan
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Florida, Jacksonville -Neurology Research Department	Jacksonville	Florida
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	Neurology Associates, P.C.	Lincoln	Nebraska
United States	UCLA Als Clinic	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Jefferson Weinberg ALS Center	Philadelphia	Pennsylvania
United States	Temple University Lewis Katz School of Medicine	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	UC Davis Health	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	University of South Florida	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma America Inc.	Massachusetts General Hospital

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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	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.	Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Secondary	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.	Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Secondary	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.	Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Secondary	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.	Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Secondary	Change from baseline in slow vital capacity.	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).
Secondary	Change from baseline in hand-held dynamometry.	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).