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

• ClinicalTrials.gov Identifier: NCT01492686
• Recruitment Status: Completed
• First Posted: December 15, 2011
• Results First Posted: December 31, 2018
• Last Update Posted: December 31, 2018
• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Information provided by (Responsible Party): Mitsubishi Tanabe Pharma Corporation

Study Description

Brief Summary:

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Study of MCI-186 for Treatment of the Patients With Amyotrophic Lateral Sclerosis (ALS) 2
• Study Start Date: December 2011
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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: 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).; 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.

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 ]
   0=worst; 48=best

Secondary Outcome Measures :

1. Number of Participants With Death or a Specified State of Disease Progression [ Time Frame: 24 weeks ]
   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.
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. 0=worst; 102=best
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, Activities of daily living (ADL) and independence, eating and drinking, communication, and emotional reactions. 200=worst; 40=best
5. Percentage of Participants With Adverse Events [ Time Frame: 24 weeks ]
6. Percentage of Participants With Adverse Drug Reactions [ Time Frame: 24 weeks ]
7. Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of "Investigations" (PT, MedDRA Ver. 17.0) [ Time Frame: 24 weeks ]
8. Percentage of Participants With Abnormal Values in Sensory Examinations [ Time Frame: baseline and 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 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.

Contacts and Locations

Locations

Japan

Osaka, Japan

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Corporation

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT01492686
• Other Study ID Numbers: MCI186-19
• First Posted: December 15, 2011
• Results First Posted: December 31, 2018
• Last Update Posted: December 31, 2018
• Last Verified: June 2018

Keywords provided by Mitsubishi Tanabe Pharma Corporation:

Amyotrophic Lateral Sclerosis (ALS)

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