Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
- Registration Number
- NCT04569084
- Lead Sponsor
- Mitsubishi Tanabe Pharma America Inc.
- Brief Summary
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:
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 384
- 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.
- Subjects will be male or female, ≥ 18 to 75 years of age at the time the ICF is signed.
- Subjects will be diagnosed with Definite ALS or Probable ALS according to the El Escorial revised criteria for the diagnosis of ALS.
- Subjects with a baseline score ≥ 2 points on each individual item of the ALSFRS- R at screening and baseline visits.
- Subjects have a screening and baseline %forced vital capacity (FVC) ≥ 70%.
- Subjects with 1- to 4-point decline for 8 weeks (±7 days) in ALSFRS-R total score between screening and baseline visits.
- Subjects whose first symptom of ALS has occurred within 2 years of providing written informed consent.
Exclusions Related to Primary Diagnosis
-
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)
-
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
-
Subjects undergoing treatment for a malignancy.
-
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.
-
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.
-
Subjects who are female, of childbearing potential, and pregnant (a positive pregnancy test) or lactating at the screening visit (Visit 1).
-
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.
-
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.
-
Subjects who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations greater than 2 times the upper limit of normal (ULN) at screening.
-
Subjects with a Glomerular Filtration Rate (GFR) < 30 mL/Min Per 1.73 m2 at screening, using the Larsson Equation.
Exclusions Related to Medications
-
Subjects with history of hypersensitivity to edaravone, any of the additives or inactive ingredients of edaravone, or sulfites.
-
Subjects with hereditary problems of fructose intolerance (eg, fructose, sucrose, invert sugar, and sorbitol).
-
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.
-
Subjects who have received any previous treatment with edaravone.
-
Subjects who have received stem cell therapy.
-
Subjects who are unable to take their medications orally at baseline (Visit 2).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MT-1186 and Placebo Placebo - MT-1186 MT-1186 - MT-1186 and Placebo MT-1186 -
- Primary Outcome Measures
Name Time Method CAFS Score at Week 48 up to 48 Weeks CAFS ranks patients' clinical outcomes based on survival time and change in the ALSFRS-R score. To calculate a patient's CAFS, each patient is compared individually to all other patients in the study. The summary score for each patient is the sum of the comparisons ( 1, 0, 1) against all other patients.
After that, patients' summary scores are ranked. The CAFS rank is 1-383 and a higher CAFS rank indicates a better outcome than does a lower CAFS.
Since CAFS were calculated using the imputed ALSFRS-R scores with multiple imputation method, and the maximum varies for each simulation, 383 is the maximum possible value of full range for measure of dispersion.
- Secondary Outcome Measures
Name Time Method Change From Baseline in % Slow Vital Capacity (SVC) at Week 48 up to 48 Weeks SVC measurements will be conducted in clinic at around the same time of day where possible with the subject in sitting upright position. Subjects should make at least 3 attempts to generate acceptable and reproducible SVC data. The highest value was selected and recorded.
Change From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ)40 at Week 48 up to 48 Weeks 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).
Time to Death, Tracheostomy or Permanent Assisted Mechanical Ventilation (≥ 23 Hours/Day) up to 48 Weeks Time to Death or PAMV (≥ 23 Hours/Day) up to 48 Weeks Time to Death up to 48 Weeks
Trial Locations
- Locations (94)
Thomas Jefferson University, Jefferson Weinberg ALS Center
🇺🇸Philadelphia, Pennsylvania, United States
UF Health Cancer Center
🇺🇸Gainesville, Florida, United States
University California Los Angeles Medical Center (UCLA)
🇺🇸Los Angeles, California, United States
Emory University - School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Wesley Neurology Clinic, P.C.
🇺🇸Cordova, Tennessee, United States
HonorHealth Neurology
🇺🇸Scottsdale, Arizona, United States
Ochsner Center for Primary Care and Wellness
🇺🇸Jefferson, Louisiana, United States
Lahey Hospital
🇺🇸Burlington, Massachusetts, United States
Neurology Associates, P.C. - Lincoln
🇺🇸Lincoln, Nebraska, United States
Saskatoon City Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Odette Cancer Center-Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Lewis Katz School of Medicine at Temple University
🇺🇸Philadelphia, Pennsylvania, United States
Las Vegas Clinic
🇺🇸Las Vegas, Nevada, United States
The University of Vermont (UVM) and UVM Medical Center National ALS Center of Excellence
🇺🇸Burlington, Vermont, United States
Nerve And Muscle Center Of Texas
🇺🇸Houston, Texas, United States
St. Luke's Rehabilitation Institute
🇺🇸Spokane, Washington, United States
Kagawa University Hospital
🇯🇵Miki-cho, Kita-gun, Kagawa, Japan
Universitaets- und Rehabilitationskliniken Ulm
🇩🇪Ulm, Germany
Niigata University Medical & Dental Hospital
🇯🇵Asahimachidori, Chuo-ku, Niigata-shi, Niigata, Japan
Saitama Neuropsychiatric Institute
🇯🇵Chuo-ku, Saitama-shi, Saitama, Japan
Georg-August-Universitaet Goettingen - Universitaetsmedizin Goettingen (UMG)
🇩🇪Goettingen, Germany
National Hospital Organization Higashinagoya National Hospital
🇯🇵Meito-ku, Nagoya-shi, Aichi, Japan
London Health Sciences Centre - University Hospital
🇨🇦London, Ontario, Canada
Medizinische Hochschule Hannover
🇩🇪Hannover, Lower Saxony, Germany
Charite Campus Virchow
🇩🇪Berlin, Germany
Istituto Nazionale Neurologico Carlo Besta
🇮🇹Milano, Italy
Recherche Sepmus, Inc
🇨🇦Greenfield Park, Quebec, Canada
Murakami Karindoh Hospital
🇯🇵Nishi-ku, Fukuoka-shi, Fukuoka, Japan
Deutsche Klinik fuer Diagnostik
🇩🇪Wiesbaden, Germany
University Medical Center Rostock
🇩🇪Rostock, Germany
Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
🇮🇹Milano, Italy
National Hospital Organization Chibahigashi National Hospital
🇯🇵Chuo-ku, Chiba-shi, Chiba, Japan
Yokohama City University Hospital
🇯🇵Kanazawa-ku, Yokohama-shi, Kanagawa, Japan
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Klinikum Rechts der Isar der Technischen Universitaet Muenchen
🇩🇪Muenchen, Germany
Policlinico A. Gemelli
🇮🇹Roma, Italy
Centro SLA di Palermo
🇮🇹Palermo, Italy
National Hospital Organization Iou National Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Hospital Organization Kumamoto Saishun Medical Center
🇯🇵Koshi-shi, Kumamoto, Japan
Kitasato University Hospital
🇯🇵Minami-ku, Sagamihara-city, Kanagawa, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Kansai Electric Power Hospital
🇯🇵Fukushima-ku, Osaka-shi, Osaka, Japan
Toho University Omori Medical Center
🇯🇵Ota-ku, Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hanyang University Medical Center
🇰🇷Seoul, Korea, Republic of
Istituto Auxologico Italiano - Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto Scientifico Ospedale San Luca
🇮🇹Modena, Italy
Centre Hospitalier De L'Universite De Montreal (Chum) Notre-Dame Hospital
🇨🇦Montreal, Quebec, Canada
Montreal Neurological Institute And Hospital
🇨🇦Montreal, Quebec, Canada
CHU de Quebec-Hopital-Enfant-Jesus
🇨🇦Quebec City, Quebec, Canada
Health Science Center Mcmaster University
🇨🇦Hamilton, Ontario, Canada
Nagoya University Hospital
🇯🇵Showa-ku, Nagoya, Aichi, Japan
Hiroshima University Hospital
🇯🇵Minami-ku, Hiroshima-shi, Hiroshima, Japan
National Hospital Organization Utano National Hospital
🇯🇵Ukyo-ku, Kyoto City, Kyoto, Japan
National Hospital Organization Hokkaido Medical Center
🇯🇵Sapporo-shi, Hokkaido, Japan
National Hospital Organization Osaka Toneyama Medical Center
🇯🇵Toyonaka-shi, Osaka, Japan
Shiga University of Medical Science Hospital
🇯🇵Otsu City, Shiga, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
St. Joseph's Hospital and Medical Center (SJHMC)
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of South Florida (USF) - Carol and Frank Morsani Center for Advanced Health Care (CAHC)
🇺🇸Tampa, Florida, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Loma Linda University Health Care - Department of Neurology
🇺🇸Loma Linda, California, United States
Woodland Research Northwest
🇺🇸Rogers, Arkansas, United States
UCSD Medical Center
🇺🇸La Jolla, California, United States
University of California Irvine (UCI) Health - Women's Healthcare Center
🇺🇸Orange, California, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
University Of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Austin Neuromuscular Center
🇺🇸Austin, Texas, United States
Sentara Neurology Specialists
🇺🇸Virginia Beach, Virginia, United States
Regional Health Authority B
🇨🇦Fredericton, New Brunswick, Canada
West Virginia University School of Medicine (WVUSoM) - Movement Disorder Clinic
🇺🇸Morgantown, West Virginia, United States
UKRUB - Berufsgenossenschaftliches Universitatsklinikum Bergmannsheil GmbH - Medizinische Klinik III
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Universitätsklinik Bonn-Motoneuronambulanz, Klinik und Poliklinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
🇩🇪Bonn, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuezburg, Germany
Universita degli Studi di Torino - Centro Regionale Esperto Per La Sclerosi Laterale Amiotrofica (CRESLA)
🇮🇹Turin, Piemonte, Italy
Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca Granda - Centro Clinico Nemo (Neuro Muscular Omnicentre)
🇮🇹Milan, Italy
Fukushima Medical University Hospital
🇯🇵Fukushima-shi, Fukushima, Japan
Tohoku University Hospital
🇯🇵Sendai-city, Miyagi, Japan
Tokyo Metropolitan Neurological Hospital
🇯🇵Fuchu-city, Tokyo, Japan
National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
🇯🇵Aoi-ku, Shizuoka-shi, Shizuoka, Japan
Teikyo University Hospital
🇯🇵Itabashi-ku, Tokyo, Japan
University hospital Bern (Inselspital)
🇨🇭Bern, BE, Switzerland
Neurocenter of Southern Switzerland
🇨🇭Lugano, Switzerland
Hopitaux Universitaires de Geneve (HUG) (Hopital Cantonal)
🇨🇭Geneve, Switzerland
Zentrumsleiter Muskelzentrum/ALS Clinic Kantonsspital St.Gallen Muskelzentrum/ALS Clinic
🇨🇭St.Gallen, Switzerland
University of Alberta - Walter C Mackenzie Health Sciences Centre (WCM)
🇨🇦Edmonton, Alberta, Canada