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

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ClinicalTrials.gov Identifier: NCT04259255
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : August 24, 2020
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Mitsubishi Tanabe Pharma America Inc.

Tracking Information
First Submitted Date January 27, 2020
First Posted Date February 6, 2020
Last Update Posted Date August 24, 2020
Actual Study Start Date October 21, 2019
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 4, 2020)
  • Change in levels of 4-hydroxynoneal (4-HNE) 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 4-HNE.
  • 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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: February 4, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
Official Title Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
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 Type Observational
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.
Condition
  • Amyotrophic Lateral Sclerosis
  • ALS
Intervention Drug: Edaravone

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 Name: Radicava®
Study Groups/Cohorts Edaravone
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: Drug: Edaravone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 4, 2020)
300
Original Estimated Enrollment Same as current
Estimated Study Completion Date February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Massachusetts General Hospital 617-724-2609 Lmtamburello@mgh.harvard.edu
Contact: Massachusetts General Hospital 617-724-4246 mdavis52@mgh.harvard.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04259255
Other Study ID Numbers REFINE-ALS
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Mitsubishi Tanabe Pharma America Inc.
Study Sponsor Mitsubishi Tanabe Pharma America Inc.
Collaborators Massachusetts General Hospital
Investigators
Principal Investigator: James Berry, MD, MPH Massachusetts General Hospital
PRS Account Mitsubishi Tanabe Pharma America Inc.
Verification Date August 2020