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

• ClinicalTrials.gov Identifier: NCT00330681
• Recruitment Status: Completed
• First Posted: May 29, 2006
• Results First Posted: May 17, 2017
• Last Update Posted: May 17, 2017
• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Information provided by (Responsible Party): Mitsubishi Tanabe Pharma Corporation

Study Description

Brief Summary:

The primary objective of this study is to confirm the efficacy of 60 mg of MCI-186 via intravenous drip once a day in 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. And in addition, this study will be performed to examine the safety of MCI-186 to ALS patients.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: MCI-186; Drug: Placebo of MCI-186	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Confirmatory Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis in Double-blind, Parallel-group, Placebo-controlled Manner.
• Study Start Date: May 2006
• Actual Primary Completion Date: September 2008
• Actual Study Completion Date: September 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; MCI-186	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). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).; Other Names: Edaravone; Radicut
Placebo Comparator: 2; Placebo of MCI-186	Drug: Placebo of MCI-186; Two ampoules of placebo injection are intravenously administered once a day, for successive 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Death or a Specified State of Disease Progression [ Time Frame: 24 weeks ]
   Any of "death, disability of independent ambulation, loss of upper arm function, tracheotomy, use of respirator, and use of tube feeding" was defined as an event.
2. Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks [ Time Frame: baseline and 24 weeks ]
3. Change From Baseline in Modified Norris Scale Score in Full Analysis Set (FAS) Population at 24 Weeks [ Time Frame: baseline and 24 weeks ]
   The Modified Norris Scale is a measure of movement disorder for patients with ALS. Worst=0, Best=102
4. Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks [ Time Frame: baseline and 24 weeks ]
   The ALSAQ40 score is a measure of QoL for patients with ALS. The ALSAQ40 evaluates domains that include physical mobility, ADL and independence, eating and drinking, communication, and emotional reactions. Worst=200, Best=40
5. Percentage of Participants With Adverse Events [ Time Frame: 24 weeks ]
6. Percentage of Participants With Adverse Drug Reactions [ Time Frame: 24 weeks ]
7. Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group [ Time Frame: 24 weeks ]
8. Percentage of Participants With Abnormal Changes in Sensory Examinations [ Time Frame: 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients who are defined as "definite ALS," "probable ALS" or "probable-laboratory-supported ALS," met diagnostic criteria revised EL Escorial for 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 3 years after the onset of ALS.
• Patients whose progress of the condition during 12 weeks before administration meet other requirements.

Exclusion Criteria:

• Patients judged to be inadequate to participate in this study by their physician, because those patients' general condition deteriorated to the point that they need to be hospitalized for severe hepatic disease, severe heart disease, severe renal disease and so on, or they need to be administered antibiotics to infection.
• Patients who complain the difficulty in breathing caused by deteriorating the respiratory function.
• 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.

Contacts and Locations

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Chair: Koji Abe, professor; Graduate School of Medicine and Dentistry, Okayama University

More Information

Publications of Results:

Abe K, Itoyama Y, Sobue G, Tsuji S, Aoki M, Doyu M, Hamada C, Kondo K, Yoneoka T, Akimoto M, Yoshino H; Edaravone ALS Study Group. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7. doi: 10.3109/21678421.2014.959024. Epub 2014 Oct 6.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00330681
• Other Study ID Numbers: MCI186-16
• First Posted: May 29, 2006
• Results First Posted: May 17, 2017
• Last Update Posted: May 17, 2017
• Last Verified: April 2017

Keywords provided by Mitsubishi Tanabe Pharma Corporation:

Amyotrophic lateral sclerosis; free radical scavenger

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Edaravone; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Physiological Effects of Drugs