Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS

A Phase 3b, Multicenter, Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Oral Edaravone Administered for a Period of 48 Weeks in Subjects With Amyotrophic Lateral Sclerosis (ALS)

To evaluate and compare the efficacy of two dosing regimens of oral edaravone in subjects with amyotrophic lateral sclerosis (ALS) based on the change in ALS Functional Rating Scale- Revised (ALSFRS-R) score from baseline up to Week 48:

Study Overview

• Status: Terminated
• Conditions: ALS
• Intervention / Treatment: Drug: MT-1186; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Desk, to prevent miscommunication,; Phone Number: please email:; Email: information@mt-pharma-us.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta - Walter C Mackenzie Health Sciences Centre (WCM)
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 0C7
      • Regional Health Authority B
  • Ontario
    • Hamilton, Ontario, Canada, L8P 1H1
      • Health Science Center Mcmaster University
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Center-Sunnybrook Health Sciences Centre
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus, Inc
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier De L'Universite De Montreal (Chum) Notre-Dame Hospital
    • Quebec City, Quebec, Canada, G1J 1Z4
      • CHU de Quebec-Hopital-Enfant-Jesus
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0M7
      • Saskatoon City Hospital
• Germany
  • Berlin, Germany, 13353
    • Charite Campus Virchow
  • Bonn, Germany, 53127
    • Universitätsklinik Bonn-Motoneuronambulanz, Klinik und Poliklinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
  • Goettingen, Germany, 37075
    • Georg-August-Universitaet Goettingen - Universitaetsmedizin Goettingen (UMG)
  • Jena, Germany, 86899
    • Universitaetsklinikum Jena
  • Muenchen, Germany, 81675
    • Klinikum Rechts der Isar der Technischen Universitaet Muenchen
  • Rostock, Germany, 18147
    • University Medical Center Rostock
  • Ulm, Germany, 89081
    • Universitaets- und Rehabilitationskliniken Ulm
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik fuer Diagnostik
  • Wuezburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44789
      • UKRUB - Berufsgenossenschaftliches Universitatsklinikum Bergmannsheil GmbH - Medizinische Klinik III
• Italy
  • Milan, Italy, Italy
    • Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca Granda - Centro Clinico Nemo (Neuro Muscular Omnicentre)
  • Milano, Italy, 20132
    • Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
  • Milano, Italy, Italy
    • Istituto Nazionale Neurologico Carlo Besta
  • Modena, Italy, 41126
    • Istituto Auxologico Italiano - Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto Scientifico Ospedale San Luca
  • Palermo, Italy, 90129
    • Centro SLA di Palermo
  • Roma, Italy, CAP 00168
    • Policlinico A. Gemelli
  • Piemonte
    • Turin, Piemonte, Italy, 10126
      • Universita degli Studi di Torino - Centro Regionale Esperto Per La Sclerosi Laterale Amiotrofica (CRESLA)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Aichi
    • Meito-ku, Nagoya-shi, Aichi, Japan, 465-8620
      • National Hospital Organization Higashinagoya National Hospital
    • Showa-ku, Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Chiba
    • Chuo-ku, Chiba-shi, Chiba, Japan, 260-8712
      • National Hospital Organization Chibahigashi National Hospital
  • Fukuoka
    • Nishi-ku, Fukuoka-shi, Fukuoka, Japan, 819-8585
      • Murakami Karindoh Hospital
  • Fukushima
    • Fukushima-shi, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital
  • Hiroshima
    • Minami-ku, Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 063-0005
      • National Hospital Organization Hokkaido Medical Center
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-0192
      • National Hospital Organization Iou National Hospital
  • Kagawa
    • Miki-cho, Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital
  • Kanagawa
    • Kanazawa-ku, Yokohama-shi, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
    • Minami-ku, Sagamihara-city, Kanagawa, Japan, 252-0375
      • Kitasato University Hospital
  • Kumamoto
    • Koshi-shi, Kumamoto, Japan, 861-1196
      • National Hospital Organization Kumamoto Saishun Medical Center
  • Kyoto
    • Ukyo-ku, Kyoto City, Kyoto, Japan, 616-8255
      • National hospital Organization Utano National Hospital
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Niigata
    • Asahimachidori, Chuo-ku, Niigata-shi, Niigata, Japan, 951-8520
      • Niigata University Medical & Dental Hospital
  • Osaka
    • Fukushima-ku, Osaka-shi, Osaka, Japan, 553-0003
      • Kansai Electric Power Hospital
    • Toyonaka-shi, Osaka, Japan, 560-8552
      • National Hospital Organization Osaka Toneyama Medical Center
  • Saitama
    • Chuo-ku, Saitama-shi, Saitama, Japan, 338-8577
      • Saitama Neuropsychiatric Institute
  • Shiga
    • Otsu City, Shiga, Japan, 520-2192
      • Shiga University of Medical Science Hospital
  • Shizuoka
    • Aoi-ku, Shizuoka-shi, Shizuoka, Japan, 420-8688
      • National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Fuchu-city, Tokyo, Japan, 183-0042
      • Tokyo Metropolitan Neurological Hospital
    • Itabashi-ku, Tokyo, Japan, 173-8606
      • Teikyo University Hospital
    • Ota-ku, Tokyo, Japan, 143-8541
      • Toho University Omori Medical Center
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 04763
    • Hanyang University Medical Center
• Switzerland
  • Geneve, Switzerland, 1205
    • Hopitaux Universitaires de Geneve (HUG) (Hopital Cantonal)
  • Lugano, Switzerland, 6903
    • Neurocenter of Southern Switzerland
  • St.Gallen, Switzerland, 9107
    • Zentrumsleiter Muskelzentrum/ALS Clinic Kantonsspital St.Gallen Muskelzentrum/ALS Clinic
  • BE
    • Bern, BE, Switzerland, 3010
      • University hospital Bern (Inselspital)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center (SJHMC)
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Neurology
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • La Jolla, California, United States, 92037-0897
      • UCSD Medical Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care - Department of Neurology
    • Los Angeles, California, United States, 90095
      • University California Los Angeles Medical Center (UCLA)
    • Orange, California, United States, 92868
      • University of California Irvine (UCI) Health - Women's Healthcare Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • Florida
    • Gainesville, Florida, United States, 32610-3633
      • UF Health Cancer Center
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Tampa, Florida, United States, 33616
      • University of South Florida (USF) - Carol and Frank Morsani Center for Advanced Health Care (CAHC)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University - School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Northwestern University Feinberg School of Medicine
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Ochsner Center for Primary Care and Wellness
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Lincoln, Nebraska, United States, 68506-2960
      • Neurology Associates, P.C. - Lincoln
  • Nevada
    • Las Vegas, Nevada, United States, 89145
      • Las Vegas Clinic
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Lewis Katz School of Medicine at Temple University
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Jefferson Weinberg ALS Center
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh Medical Center
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Wesley Neurology Clinic, P.C.
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
    • Houston, Texas, United States, 77019
      • Nerve and Muscle Center of Texas
  • Vermont
    • Burlington, Vermont, United States, 05401-3456
      • The University of Vermont (UVM) and UVM Medical Center National ALS Center of Excellence
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Neurology Specialists
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • St. Luke's Rehabilitation Institute
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9180
      • West Virginia University School of Medicine (WVUSoM) - Movement Disorder Clinic
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must provide a signed and dated informed consent form (ICF) to participate in the study. Subjects must be able (in the judgment of the Investigator) to understand the nature of the study and all risks involved with participation in the study. Subjects must be willing to cooperate and comply with all protocol restrictions and requirements.
2. Subjects will be male or female, ≥ 18 to 75 years of age at the time the ICF is signed.
3. Subjects will be diagnosed with Definite ALS or Probable ALS according to the El Escorial revised criteria for the diagnosis of ALS.
4. Subjects with a baseline score ≥ 2 points on each individual item of the ALSFRS- R at screening and baseline visits.
5. Subjects have a screening and baseline %forced vital capacity (FVC) ≥ 70%.
6. Subjects with 1- to 4-point decline for 8 weeks (±7 days) in ALSFRS-R total score between screening and baseline visits.
7. Subjects whose first symptom of ALS has occurred within 2 years of providing written informed consent.

Exclusion Criteria:

Exclusions Related to Primary Diagnosis

1. Subjects with a history of spinal surgery after the onset of ALS, such as surgery for cervical spondylosis or a herniated disc, or plans for such surgery during the study period.

   Exclusions Related to Other Neurological Disorders (including, but not limited to the following)

2. Subjects with the possibility that the current symptoms may be symptoms of a disease requiring differential diagnosis, such as cervical spondylosis and multifocal motor neuropathy, cannot be ruled out.

   Exclusions Related to General Health or Concomitant Conditions

3. Subjects undergoing treatment for a malignancy.
4. Subjects with a complication that could have a significant effect on efficacy evaluations, such as Parkinson's disease or syndrome, schizophrenia, bipolar disorder, and dementia.
5. Subjects who have the presence or history of any clinically significant (CS) disease (except ALS) that could interfere with the objectives of the study (the assessment of safety and efficacy) or the safety of the subject, as judged by the Investigator.
6. Subjects who are female, of childbearing potential, and pregnant (a positive pregnancy test) or lactating at the screening visit (Visit 1).
7. Subjects of childbearing potential unwilling to use acceptable method of contraception from the screening visit until 3 months after the last dose of study medication. Subjects who are sexually active who do not agree to use contraception during the study period.
8. Subjects who have a significant risk of suicidality. Subjects with any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without a specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the 3 months before the screening visit.
9. Subjects who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations greater than 2 times the upper limit of normal (ULN) at screening.

10. Subjects with a Glomerular Filtration Rate (GFR) < 30 mL/Min Per 1.73 m2 at screening, using the Larsson Equation.

    Exclusions Related to Medications

11. Subjects with history of hypersensitivity to edaravone, any of the additives or inactive ingredients of edaravone, or sulfites.
12. Subjects with hereditary problems of fructose intolerance (eg, fructose, sucrose, invert sugar, and sorbitol).
13. Subjects who participated in another study and were administered an investigational product within 1 month or 5 half-lives of the investigational agent, whichever is longer, before providing informed consent for the present study.
14. Subjects who have received any previous treatment with edaravone.
15. Subjects who have received stem cell therapy.
16. Subjects who are unable to take their medications orally at baseline (Visit 2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT-1186	Drug: MT-1186; Oral edaravone; Other Names: Oral edaravone
Experimental: MT-1186 and Placebo	Drug: MT-1186; Oral edaravone; Other Names: Oral edaravone; Drug: Placebo; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ALS Functional Rating Scale- Revised (ALSFRS-R) score from baseline to Week 48 of treatment	The ALSFRS-R is rating scale (ratings 0 = can't do, to 4 = normal ability) used to determine participants' assessment of their capability and independence in 12 functional activities.	up to 48 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in % slow vital capacity (SVC) at Week 48		up to 48 Weeks
Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ)40 at Week 48	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, ranging from 0 (best health as assessed by the scale) to 100 (worse health as assessed by the measure).	up to 48 Weeks

Other Outcome Measures

Outcome Measure	Time Frame
Time to death, tracheostomy or permanent assisted mechanical ventilation (≥ 23 hours/day)	up to 48 Weeks

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma America Inc.
• Investigators: Study Director: Head of Medical Science, Mitsubishi Tanabe Pharma America Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): September 29, 2023
• Study Completion (Actual): September 29, 2023

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MT-1186-A02; jRCT2031200301 (Registry Identifier: Japan Registry of Clinical Trials (jRCT)); 2019-004256-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No