Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Amyotrophic Lateral Sclerosis (ALS)
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.
Interventions
DRUGMCI-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).
DRUGPlacebo
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).
DRUGMCI-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.
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | baseline and 24 weeks | 0=worst; 48=best |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death or a Specified State of Disease Progression | 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. |
| 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 | baseline and 24 weeks | The Modified Norris Scale is a measure of movement disorder for patients with ALS. 0=worst; 102=best |
| Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks | 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 |
| 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 | — |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-186 Double-blind MCI-186, Then Open-label MCI-186. 2 ampoules of edaravone injection 30 mg were administered once daily over 60 min by intravenous infusion. | 69 |
| Placebo of MCI-186 Double-blind Placebo of MCI-186, Then Open-label MCI-186. 2 ampoules of edaravone injection placebo were administered once daily over 60 min by intravenous infusion. | 68 |
| Total | 137 |
Baseline characteristics
| Characteristic | MCI-186 | Placebo of MCI-186 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 22 Participants | 45 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 46 Participants | 92 Participants |
| Sex: Female, Male Female | 31 Participants | 27 Participants | 58 Participants |
| Sex: Female, Male Male | 38 Participants | 41 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| other Total, other adverse events | 57 / 69 | 51 / 68 | 53 / 65 | 48 / 58 |
| serious Total, serious adverse events | 11 / 69 | 16 / 68 | 17 / 65 | 23 / 58 |
Outcome results
Primary
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
Time frame: baseline and 24 weeks
Population: 1 patient who did not reach the end of cycle 3 was excluded from the FAS in the MCI-186 group.~2 patients who did not reach the end of cycle 3 were excluded from the FAS in the Placebo of MCI-186 group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 | Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | -5.01 units on a scale | Standard Error 0.64 |
| Placebo of MCI-186 | Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | -7.5 units on a scale | Standard Error 0.66 |
Secondary
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
Time frame: baseline and 24 weeks
Population: 1 patient who did not reach the end of cycle 3 was excluded from the FAS in the MCI-186 group.~2 patients who did not reach the end of cycle 3 and 2 patient with missing data were excluded from the FAS in the Placebo of MCI-186 group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 | Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks | 17.25 units on a scale | Standard Error 3.39 |
| Placebo of MCI-186 | Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks | 26.04 units on a scale | Standard Error 3.53 |
Secondary
Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks
Time frame: baseline and 24 weeks
Population: 1 patient who did not reach the end of cycle 3 and 1 patient with missing data were excluded from the FAS in the MCI-186 group.~2 patients who did not reach the end of cycle 3 were excluded from the FAS in the Placebo of MCI-186 group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -15.61 percentage of FVC | Standard Error 2.41 |
| Placebo of MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -20.4 percentage of FVC | Standard Error 2.48 |
Secondary
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
Time frame: baseline and 24 weeks
Population: 1 patient who did not reach the end of cycle 3 was excluded from the FAS in the MCI-186 group.~2 patients who did not reach the end of cycle 3 and 3 patient with missing data were excluded from the FAS in the Placebo of MCI-186 group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 | Change From Baseline in Modified Norris Scale Score in Full Analysis Set (FAS) Population at 24 Weeks | -15.91 units on a scale | Standard Error 1.97 |
| Placebo of MCI-186 | Change From Baseline in Modified Norris Scale Score in Full Analysis Set (FAS) Population at 24 Weeks | -20.8 units on a scale | Standard Error 2.06 |
Secondary
Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0)
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Blood bilirubin increased | 0 percentage of Participants |
| MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Blood creatine phosphokinase increased | 0 percentage of Participants |
| MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Liver function test abnormal | 1.4 percentage of Participants |
| MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | White blood cell count decreased | 1.4 percentage of Participants |
| Placebo of MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | White blood cell count decreased | 0 percentage of Participants |
| Placebo of MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Blood bilirubin increased | 1.5 percentage of Participants |
| Placebo of MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Liver function test abnormal | 1.5 percentage of Participants |
| Placebo of MCI-186 | Laboratory Tests Percentage of Participants With Adverse Events by System Organ Class (SOC) of Investigations (PT, MedDRA Ver. 17.0) | Blood creatine phosphokinase increased | 1.5 percentage of Participants |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Loss of upper limbs function | 0 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Use of respirator | 0 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Disability of independent ambulation | 0 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Use of tube feeding | 0 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Tracheotomy | 1 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Loss of useful speech | 1 Count of Participants |
| MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Death | 0 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Loss of useful speech | 3 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Death | 0 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Disability of independent ambulation | 2 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Loss of upper limbs function | 0 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Tracheotomy | 0 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Use of respirator | 0 Count of Participants |
| Placebo of MCI-186 | Number of Participants With Death or a Specified State of Disease Progression | Use of tube feeding | 1 Count of Participants |
Secondary
Percentage of Participants With Abnormal Values in Sensory Examinations
Time frame: baseline and 24 weeks
Population: A note:~Four patients of Placebo of MCI-186 group did not have data at 24 week. Therefore, concerning numbness (at 24 week) and staggering (at 24 week), the number of participants analysed are 64 in the both groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Numbness (at baseline) | 2.9 percentage of Participants |
| MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Numbness (at 24 week) | 7.2 percentage of Participants |
| MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Staggering (at baseline) | 1.4 percentage of Participants |
| MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Staggering (at 24 week) | 2.9 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Staggering (at 24 week) | 3.1 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Numbness (at baseline) | 7.4 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Staggering (at baseline) | 8.8 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Values in Sensory Examinations | Numbness (at 24 week) | 9.4 percentage of Participants |
Secondary
Percentage of Participants With Adverse Drug Reactions
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 | Percentage of Participants With Adverse Drug Reactions | 2.9 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Drug Reactions | 7.4 percentage of Participants |
Secondary
Percentage of Participants With Adverse Events
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 | Percentage of Participants With Adverse Events | 84.1 percentage of Participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Events | 83.8 percentage of Participants |