Clinical trial NCT04569084: Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: ALS
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-29
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:


Eligibility criteria: 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).

Primary outcomes:
measure: CAFS Score at Week 48
timeFrame: up to 48 Weeks
Secondary outcomes:
measure: Change From Baseline in % Slow Vital Capacity (SVC) at Week 48
timeFrame: up to 48 Weeks
measure: Change From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ)40 at Week 48
timeFrame: up to 48 Weeks
measure: Time to Death, Tracheostomy or Permanent Assisted Mechanical Ventilation (≥ 23 Hours/Day)
timeFrame: up to 48 Weeks
measure: Time to Death or PAMV (≥ 23 Hours/Day)
timeFrame: up to 48 Weeks
measure: Time to Death
timeFrame: up to 48 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center (SJHMC)
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care - Department of Neurology
state: California
city: Los Angeles
country: United States
facility: University California Los Angeles Medical Center (UCLA)
state: California
city: Orange
country: United States
facility: University of California Irvine (UCI) Health - Women's Healthcare Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Gainesville
country: United States
facility: UF Health Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: University of South Florida (USF) - Carol and Frank Morsani Center for Advanced Health Care (CAHC)
state: Florida
city: Atlanta
country: United States
facility: Emory University - School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Jefferson
country: United States
facility: Ochsner Center for Primary Care and Wellness
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lincoln
country: United States
facility: Neurology Associates, P.C. - Lincoln
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Jefferson Weinberg ALS Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh Medical Center
state: Pennsylvania
city: Cordova
country: United States
facility: Wesley Neurology Clinic, P.C.
state: Tennessee
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Houston
country: United States
facility: Nerve And Muscle Center Of Texas
state: Texas
city: Burlington
country: United States
facility: The University of Vermont (UVM) and UVM Medical Center National ALS Center of Excellence
state: Vermont
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: St. Luke's Rehabilitation Institute
state: Washington
city: Morgantown
country: United States
facility: West Virginia University School of Medicine (WVUSoM) - Movement Disorder Clinic
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta - Walter C Mackenzie Health Sciences Centre (WCM)
state: Alberta
city: Fredericton
country: Canada
facility: Regional Health Authority B
state: New Brunswick
city: Hamilton
country: Canada
facility: Health Science Center Mcmaster University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Center-Sunnybrook Health Sciences Centre
state: Ontario
city: Greenfield Park
country: Canada
facility: Recherche Sepmus, Inc
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier De L'Universite De Montreal (Chum) Notre-Dame Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute And Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-Hopital-Enfant-Jesus
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital
state: Saskatchewan
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Lower Saxony
city: Bochum
country: Germany
facility: UKRUB - Berufsgenossenschaftliches Universitatsklinikum Bergmannsheil GmbH - Medizinische Klinik III
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charite Campus Virchow
city: Bonn
country: Germany
facility: Universitätsklinik Bonn-Motoneuronambulanz, Klinik und Poliklinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
city: Goettingen
country: Germany
facility: Georg-August-Universitaet Goettingen - Universitaetsmedizin Goettingen (UMG)
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universitaet Muenchen
city: Rostock
country: Germany
facility: University Medical Center Rostock
city: Ulm
country: Germany
facility: Universitaets- und Rehabilitationskliniken Ulm
city: Wiesbaden
country: Germany
facility: Deutsche Klinik fuer Diagnostik
city: Wuezburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Turin
country: Italy
facility: Universita degli Studi di Torino - Centro Regionale Esperto Per La Sclerosi Laterale Amiotrofica (CRESLA)
state: Piemonte
city: Milano
country: Italy
facility: Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
city: Milano
country: Italy
facility: Istituto Nazionale Neurologico Carlo Besta
city: Milan
country: Italy
facility: Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca Granda - Centro Clinico Nemo (Neuro Muscular Omnicentre)
city: Modena
country: Italy
facility: Istituto Auxologico Italiano - Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto Scientifico Ospedale San Luca
city: Palermo
country: Italy
facility: Centro SLA di Palermo
city: Roma
country: Italy
facility: Policlinico A. Gemelli
city: Meito-ku, Nagoya-shi
country: Japan
facility: National Hospital Organization Higashinagoya National Hospital
state: Aichi
city: Showa-ku, Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Chuo-ku, Chiba-shi
country: Japan
facility: National Hospital Organization Chibahigashi National Hospital
state: Chiba
city: Nishi-ku, Fukuoka-shi
country: Japan
facility: Murakami Karindoh Hospital
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Minami-ku, Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Medical Center
state: Hokkaido
city: Kanazawa-shi
country: Japan
facility: National Hospital Organization Iou National Hospital
state: Ishikawa
city: Miki-cho, Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Kanazawa-ku, Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Minami-ku, Sagamihara-city
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Koshi-shi
country: Japan
facility: National Hospital Organization Kumamoto Saishun Medical Center
state: Kumamoto
city: Ukyo-ku, Kyoto City
country: Japan
facility: National Hospital Organization Utano National Hospital
state: Kyoto
city: Sendai-city
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Asahimachidori, Chuo-ku, Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital
state: Niigata
city: Fukushima-ku, Osaka-shi
country: Japan
facility: Kansai Electric Power Hospital
state: Osaka
city: Toyonaka-shi
country: Japan
facility: National Hospital Organization Osaka Toneyama Medical Center
state: Osaka
city: Chuo-ku, Saitama-shi
country: Japan
facility: Saitama Neuropsychiatric Institute
state: Saitama
city: Otsu City
country: Japan
facility: Shiga University of Medical Science Hospital
state: Shiga
city: Aoi-ku, Shizuoka-shi
country: Japan
facility: National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Fuchu-city
country: Japan
facility: Tokyo Metropolitan Neurological Hospital
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Teikyo University Hospital
state: Tokyo
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Bern
country: Switzerland
facility: University hospital Bern (Inselspital)
state: BE
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve (HUG) (Hopital Cantonal)
city: Lugano
country: Switzerland
facility: Neurocenter of Southern Switzerland
city: St.Gallen
country: Switzerland
facility: Zentrumsleiter Muskelzentrum/ALS Clinic Kantonsspital St.Gallen Muskelzentrum/ALS Clinic
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science
role: STUDY_DIRECTOR
References: