Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis

Efficacy and Safety Study of MCI-186 for Treatment of the Patients With Amyotrophic Lateral Sclerosis (ALS) 2

The primary objective of the study is to confirm the efficacy of 60 mg of MCI-186 via intravenous drip infusion once a day in the patients with ALS based on the changes in the revised ALS functional rating scale (ALSFRS-R) scores after 24 weeks administration in double-blind, placebo-controlled manner. The study is also to examine the safety of MCI-186 to the ALS patients.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: MCI-186; Drug: MCI-186 in open label phase; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients whose conditions are defined as "definite ALS"or "probable ALS"diagnostic criteria El Escorial and revised Airlie House.
• Patients who can eat a meal, excrete, or move with oneself alone, and do not need assistance in everyday life.
• Patients of less than 2 years after the onset of ALS.
• Patients whose progress of the condition during 12 weeks before administration meet other requirements.

Exclusion Criteria:

• Patients with such complications as Parkinson's disease, schizophrenia, dementia, renal failure, or other severe complication, and patients who have the anamnesis of hypersensitivity to edaravone.
• Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant, and patients who can not agree to contraception.
• Patients who have participated in other trials within 12 weeks before consent, or who are participating in other clinical trials at present.
• In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: MCI-186; Two ampoules (60 mg) of MCI-186 injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). The following treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).; Drug: MCI-186 in open label phase; All patients after the double blind phase may receive MCI-186 in 7th until 12th treatment - observation cycles at the patients' will.
PLACEBO_COMPARATOR: Arm 2	Drug: MCI-186 in open label phase; All patients after the double blind phase may receive MCI-186 in 7th until 12th treatment - observation cycles at the patients' will.; Drug: Placebo; Two ampoules of placebo injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). The following treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks	0=worst; 48=best	baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Death or a Specified State of Disease Progression	Any of "death, disability of independent ambulation, loss of upper limbs function, tracheotomy, use of respirator, use of tube feeding and loss of useful speech" was defined as an event.	24 weeks
Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks		baseline and 24 weeks
Change From Baseline in Modified Norris Scale Score in Full Analysis Set (FAS) Population at 24 Weeks	The Modified Norris Scale is a measure of movement disorder for patients with ALS. 0=worst; 102=best	baseline and 24 weeks
Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks	The ALSAQ40 score is a measure of QoL for patients with ALS. The ALSAQ40 evaluates domains that include physical mobility, Activities of daily living (ADL) and independence, eating and drinking, communication, and emotional reactions. 200=worst; 40=best	baseline and 24 weeks
Percentage of Participants With Adverse Events		24 weeks
Percentage of Participants With Adverse Drug Reactions		24 weeks
Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of "Investigations" (PT, MedDRA Ver. 17.0)		24 weeks
Percentage of Participants With Abnormal Values in Sensory Examinations		baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017 Jul;16(7):505-512. doi: 10.1016/S1474-4422(17)30115-1. Epub 2017 May 15.
• WRITING GROUP ON BEHALF OF THE EDARAVONE (MCI-186) ALS 19 STUDY GROUP. Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct;18(sup1):55-63. doi: 10.1080/21678421.2017.1364269.
• Takei K, Takahashi F, Liu S, Tsuda K, Palumbo J. Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct;18(sup1):49-54. doi: 10.1080/21678421.2017.1361443.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: December 11, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (ESTIMATE): December 15, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 31, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis (ALS)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MCI186-19