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

ALS Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04569084
• Other study ID #: MT-1186-A02
• Secondary ID: jRCT203120030120
• Status: Terminated
• Phase: Phase 3
• Start date: November 13, 2020
• Est. completion date: September 29, 2023

Study information

• Verified date: October 2023
• Source: Mitsubishi Tanabe Pharma America Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 384
• Est. completion date: September 29, 2023
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• ALS

Intervention

Drug:
• MT-1186
Oral edaravone
• Placebo
Oral

Locations

Country	Name	City	State
Canada	University of Alberta - Walter C Mackenzie Health Sciences Centre (WCM)	Edmonton	Alberta
Canada	Regional Health Authority B	Fredericton	New Brunswick
Canada	Recherche Sepmus, Inc	Greenfield Park	Quebec
Canada	Health Science Center Mcmaster University	Hamilton	Ontario
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	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	Saskatoon City Hospital	Saskatoon	Saskatchewan
Canada	Odette Cancer Center-Sunnybrook Health Sciences Centre	Toronto	Ontario
Germany	Charite Campus Virchow	Berlin
Germany	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	Georg-August-Universitaet Goettingen - Universitaetsmedizin Goettingen (UMG)	Goettingen
Germany	Medizinische Hochschule Hannover	Hannover	Lower Saxony
Germany	Universitaetsklinikum Jena	Jena
Germany	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	Muenchen
Germany	University Medical Center Rostock	Rostock
Germany	Universitaets- und Rehabilitationskliniken Ulm	Ulm
Germany	Deutsche Klinik fuer Diagnostik	Wiesbaden
Germany	Universitaetsklinikum Wuerzburg	Wuezburg
Italy	Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca Granda - Centro Clinico Nemo (Neuro Muscular Omnicentre)	Milan
Italy	Istituto Nazionale Neurologico Carlo Besta	Milano
Italy	Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)	Milano
Italy	Istituto Auxologico Italiano - Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto Scientifico Ospedale San Luca	Modena
Italy	Centro SLA di Palermo	Palermo
Italy	Policlinico A. Gemelli	Roma
Italy	Universita degli Studi di Torino - Centro Regionale Esperto Per La Sclerosi Laterale Amiotrofica (CRESLA)	Turin	Piemonte
Japan	National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders	Aoi-ku, Shizuoka-shi	Shizuoka
Japan	Niigata University Medical & Dental Hospital	Asahimachidori, Chuo-ku, Niigata-shi	Niigata
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	Chiba University Hospital	Chiba
Japan	National Hospital Organization Chibahigashi National Hospital	Chuo-ku, Chiba-shi	Chiba
Japan	Saitama Neuropsychiatric Institute	Chuo-ku, Saitama-shi	Saitama
Japan	Tokyo Metropolitan Neurological Hospital	Fuchu-city	Tokyo
Japan	Kansai Electric Power Hospital	Fukushima-ku, Osaka-shi	Osaka
Japan	Fukushima Medical University Hospital	Fukushima-shi	Fukushima
Japan	Teikyo University Hospital	Itabashi-ku	Tokyo
Japan	Yokohama City University Hospital	Kanazawa-ku, Yokohama-shi	Kanagawa
Japan	National Hospital Organization Iou National Hospital	Kanazawa-shi	Ishikawa
Japan	National Hospital Organization Kumamoto Saishun Medical Center	Koshi-shi	Kumamoto
Japan	National Hospital Organization Higashinagoya National Hospital	Meito-ku, Nagoya-shi	Aichi
Japan	Kagawa University Hospital	Miki-cho, Kita-gun	Kagawa
Japan	Hiroshima University Hospital	Minami-ku, Hiroshima-shi	Hiroshima
Japan	Kitasato University Hospital	Minami-ku, Sagamihara-city	Kanagawa
Japan	Murakami Karindoh Hospital	Nishi-ku, Fukuoka-shi	Fukuoka
Japan	Toho University Omori Medical Center	Ota-ku	Tokyo
Japan	Shiga University of Medical Science Hospital	Otsu City	Shiga
Japan	National Hospital Organization Hokkaido Medical Center	Sapporo-shi	Hokkaido
Japan	Tohoku University Hospital	Sendai-city	Miyagi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Nagoya University Hospital	Showa-ku, Nagoya	Aichi
Japan	National Hospital Organization Osaka Toneyama Medical Center	Toyonaka-shi	Osaka
Japan	National Hospital Organization Utano National Hospital	Ukyo-ku, Kyoto City	Kyoto
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Switzerland	University hospital Bern (Inselspital)	Bern	BE
Switzerland	Hopitaux Universitaires de Geneve (HUG) (Hopital Cantonal)	Geneve
Switzerland	Neurocenter of Southern Switzerland	Lugano
Switzerland	Zentrumsleiter Muskelzentrum/ALS Clinic Kantonsspital St.Gallen Muskelzentrum/ALS Clinic	St.Gallen
United States	Dent Neurologic Institute	Amherst	New York
United States	Emory University - School of Medicine	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Austin Neuromuscular Center	Austin	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Lahey Hospital	Burlington	Massachusetts
United States	The University of Vermont (UVM) and UVM Medical Center National ALS Center of Excellence	Burlington	Vermont
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Wesley Neurology Clinic, P.C.	Cordova	Tennessee
United States	UF Health Cancer Center	Gainesville	Florida
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Nerve And Muscle Center Of Texas	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Ochsner Center for Primary Care and Wellness	Jefferson	Louisiana
United States	UCSD Medical Center	La Jolla	California
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	Neurology Associates, P.C. - Lincoln	Lincoln	Nebraska
United States	Loma Linda University Health Care - Department of Neurology	Loma Linda	California
United States	University California Los Angeles Medical Center (UCLA)	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University School of Medicine (WVUSoM) - Movement Disorder Clinic	Morgantown	West Virginia
United States	University of California Irvine (UCI) Health - Women's Healthcare Center	Orange	California
United States	Lewis Katz School of Medicine at Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Jefferson Weinberg ALS Center	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center (SJHMC)	Phoenix	Arizona
United States	University Of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Woodland Research Northwest	Rogers	Arkansas
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	St. Luke's Rehabilitation Institute	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of South Florida (USF) - Carol and Frank Morsani Center for Advanced Health Care (CAHC)	Tampa	Florida
United States	Sentara Neurology Specialists	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma America Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  Japan,  Korea, Republic of,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to death, tracheostomy or permanent assisted mechanical ventilation (= 23 hours/day)		up to 48 Weeks
Primary	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	Change from baseline in % slow vital capacity (SVC) at Week 48		up to 48 Weeks
Secondary	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