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

Study Overview
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Brief Summary
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To evaluate and compare the efficacy of two dosing regimens of oral edaravone in subjects with amyotrophic lateral sclerosis (ALS), based on the time from the randomization date in Study MT-1186-A02 to at least a 12-point decrease in Revised ALS Functional Rating Score (ALSFRS-R) or death, whichever happens first, over the course of the study or until oral edaravone is commercially available in that country

Official Title
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A Phase 3b, Multicenter, Randomized, Double-blind Extension Study to Evaluate the Continued Efficacy and Safety of Oral Edaravone Administered for an Additional Period of up to 48 Weeks Following Study MT-1186-A02 in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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ALS

Intervention / Treatment
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* Drug: MT-1186
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects or their legally authorized representative must provide a signed and dated informed consent form 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 must have successfully completed all Study MT-1186-A02 visits and have been compliant with study drug. Exclusion Criteria: Subjects of childbearing potential unwilling to use an acceptable method of contraception from the Day 1/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 are female, of childbearing potential, and pregnant (a positive pregnancy test) or lactating at the Day 1/screening visit. Subjects who have a significant risk of suicide. 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) at Week 48 of Study MT-1186-A02. Subjects who are not eligible to continue in the study, as judged by the Investigator in conjunction with the MTDA medical monitor. Subjects who are unable to take their medications orally or through a PEG/RIG tube.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-1186 - Group 1<br>Oral edaravone administered once daily for up to 48 weeks or until the drug is commercially available in that country. | Drug: MT-1186<br>* Oral edaravone<br>* Other names: Oral edaravone;|
| Experimental: MT-1186 - Group 2<br>Oral edaravone administered for 10 days followed by 18-day placebo (regimen denoted as on/off) for up to 48 weeks or until the drug is commercially available in that country. | Drug: MT-1186<br>* Oral edaravone<br>* Other names: Oral edaravone;Drug: Placebo<br>* Oral<br>* Other names: Oral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from the randomization date in Study MT-1186-A02 to at least a 12-point decrease in ALSFRS-R or death, whichever happens first. | 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 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Combined Assessment of Function and Survival (CAFS) score at all visits from baseline in Study MT-1186-A02 to the end of Study MT-1186-A04 | CAFS analysis ranks clinical outcomes on the basis of survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. A subject's score will be calculated by comparing each subject to every other subject within each treatment group in the study, resulting in a score of +1 if the outcome was better than the subject being compared, -1 if worse, and 0 if the same. The subject's score will then be calculated by summing up their comparison to all of the other subjects within each treatment group in the study as CAFS score. Patients' summary scores are ranked; a higher score indicates a better performance. The score range is from 1 to N, where N is the total sample size. | Up to 96 weeks | 
| Change in the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 score at all visits from baseline in Study MT-1186-A02 to the end of Study MT-1186-A04 | 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 96 weeks | 
| Change in ALSFRS-R score at all visits from baseline in Study MT-1186-A02 to the end of Study MT-1186-A04 | 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 96 weeks | 
| Time from the randomization date in Study MT-1186-A02 to death, tracheostomy, or permanent assisted mechanical ventilation (≥23 hours/day) |  | Up to 96 weeks | 
| Time from the randomization date in Study MT-1186-A02 to death or permanent assisted mechanical ventilation (>23 hours/day) |  | Up to 96 weeks | 
| Time from the randomization date in Study MT-1186-A02 to death |  | Up to 96 weeks |