Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 74
- Locations
- 20
- Primary Endpoint
- Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration.
Study Overview
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.
Study Design
- Study Type
- Observational
- Observational Model
- Other
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Edaravone (Radicava®/Radicava ORS®) (Drug)
Outcomes
Primary Outcomes
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 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 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 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 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.
Secondary Outcomes
- Change from baseline in slow vital capacity.(Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).)
- 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 hand-held dynamometry.(Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days).)