Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Amyotrophic lateral sclerosis, free radical scavenger
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.
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). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated five times (2nd-6th cycles).
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).
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 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
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 | ALSFRS-R Score: 0=worst; 48=best |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death or a Specified State of Disease Progression | 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. |
| 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. Worst=0, Best=102 |
| 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, ADL and independence, eating and drinking, communication, and emotional reactions. Worst=200, Best=40 |
| Percentage of Participants With Adverse Events | 24 weeks | — |
| Percentage of Participants With Adverse Drug Reactions | 24 weeks | — |
| Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | 24 weeks | — |
| Percentage of Participants With Abnormal Changes in Sensory Examinations | 24 weeks | — |
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-186 Edaravone 60 mg, intravenously infused over 60 min once daily. | 102 |
| Placebo of MCI-186 Edaravone matched placebo, intravenously infused over 60 min once daily. | 104 |
| Total | 206 |
Baseline characteristics
| Characteristic | MCI-186 | Placebo of MCI-186 | Total |
|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 28 Participants | 33 Participants | 61 Participants |
| Age, Customized Between 19 and 64 years | 74 Participants | 71 Participants | 145 Participants |
| Sex: Female, Male Female | 38 Participants | 35 Participants | 73 Participants |
| Sex: Female, Male Male | 64 Participants | 69 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 88 / 102 | 91 / 104 |
| serious Total, serious adverse events | 18 / 102 | 24 / 104 |
Outcome results
Primary
Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks
ALSFRS-R Score: 0=worst; 48=best
Time frame: baseline and 24 weeks
Population: 1 patient with diseases other than ALS and 1 patient who did not reach the end of cycle 3 were excluded from the FAS in the MCI-186 group.~5 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 | -5.7 units on a scale | Standard Error 0.85 |
| 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 | -6.35 units on a scale | Standard Error 0.84 |
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, ADL and independence, eating and drinking, communication, and emotional reactions. Worst=200, Best=40
Time frame: baseline and 24 weeks
Population: 1 patient with diseases other than ALS, 1 patient who did not reach the end of cycle 3 and 5 patients with missing data were excluded from the FAS in the MCI-186 group.~5 patients who did not reach the end of cycle 3 and 4 patients 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 | 19.6 units on a scale | Standard Error 3.82 |
| Placebo of MCI-186 | Change From Baseline in ALS Assessment Questionnaire (40 Items) (ALSAQ40) in Full Analysis Set (FAS) Population at 24 Weeks | 19.13 units on a scale | Standard Error 3.79 |
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 with diseases other than ALS and 1 patient who did not reach the end of cycle 3 were excluded from the FAS in the MCI-186 group.~5 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 | -14.57 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 | -17.49 percentage of FVC | Standard Error 2.39 |
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. Worst=0, Best=102
Time frame: baseline and 24 weeks
Population: 1 patient with diseases other than ALS, 1 patient who did not reach the end of cycle 3 and 5 patients with missing data were excluded from the FAS in the MCI-186 group.~5 patients who did not reach the end of cycle 3 and 2 patients 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 | -14.12 units on a scale | Standard Error 2.05 |
| Placebo of MCI-186 | Change From Baseline in Modified Norris Scale Score in Full Analysis Set (FAS) Population at 24 Weeks | -16.15 units on a scale | Standard Error 2 |
Secondary
Death or a Specified State of Disease Progression
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.
Time frame: 24 weeks
Population: 1 patient with diseases other than ALS was excluded from the FAS in the MCI-186 group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Death or a Specified State of Disease Progression | death | 2 participants |
| MCI-186 | Death or a Specified State of Disease Progression | disability of independent ambulation | 28 participants |
| MCI-186 | Death or a Specified State of Disease Progression | loss of upper arm function | 2 participants |
| MCI-186 | Death or a Specified State of Disease Progression | tracheotomy | 0 participants |
| MCI-186 | Death or a Specified State of Disease Progression | use of respirator | 1 participants |
| MCI-186 | Death or a Specified State of Disease Progression | use of tube feeding | 5 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | use of respirator | 3 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | death | 2 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | tracheotomy | 2 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | disability of independent ambulation | 23 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | use of tube feeding | 3 participants |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | loss of upper arm function | 4 participants |
Secondary
Percentage of Participants With Abnormal Changes in Sensory Examinations
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 1 percentage of participants |
| MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 2 percentage of participants |
| MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 0 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 1 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 3.8 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 1 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 | 13.7 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Drug Reactions | 19.2 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 | 89.2 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Events | 88.5 percentage of participants |
Secondary
Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group
Time frame: 24 weeks
Population: 1 patient with missing data was excluded from the FAS in the Placebo of MCI-186 group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | White blood cell count | 2 percentage of participants |
| MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | urinary glucose | 6.9 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | White blood cell count | 5.8 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group | urinary glucose | 2.9 percentage of participants |