Clinical trial NCT04259255: Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
Official title: Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
ALS
Keywords: biomarkers
edaravone
Radicava®
Radicava ORS®
motor neuron disease
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
Collaborators: name: Massachusetts General Hospital
First posted: 2020-02-06
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of 3-nitrotyrosine (3-NT) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of urate as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of matrix metalloproteinase-9 (MMP-9) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of urinary neutrophin receptor p75 as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of neurofilaments (Nf) (Heavy and Light) as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change in levels of creatinine as a potential biomarkers of oxidative stress, inflammation or neurodegeneration.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Secondary outcomes:
measure: Change from baseline in the ALSFRS-R (ALS Functional Rating Scale .Revised) Score
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change from baseline in the King's Clinical Staging.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change from baseline in the ALSAQ-40 (ALS Assessment Questionnaire).
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change from baseline in the Appel ALS Score.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change from baseline in slow vital capacity.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
measure: Change from baseline in hand-held dynamometry.
timeFrame: Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Als Clinic
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville -Neurology Research Department
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Mercy Health
state: Michigan
city: Lincoln
country: United States
facility: Neurology Associates, P.C.
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Philadelphia
country: United States
facility: Jefferson Weinberg ALS Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Lewis Katz School of Medicine
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: SunnyBrook Research Institute
state: Ontario
Study officials:
affiliation: Massachusetts General Hospital
name: James Berry, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.