Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Amyotrophic lateral sclerosis, free radical scavenger
Brief summary
The primary objective of this study is to evaluate the efficacy of 60mg of MCI-186 via intravenous drip once a day in patients with ALS whose severity is classified as grade III, 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 who met severity classification III.
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 cannot take at least one action of eating a meal, excreting, or moving with oneself alone, and need assistance in everyday life. * 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, sever heart disease, sever 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 been administered other investigational products 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 | No primary endpoint was used, because various exploratory analyses were performed. 0=worst; 48=best |
| Death or a Specified State of Disease Progression | 24 weeks | No primary endpoint was used, because various exploratory analyses were performed. 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 | No primary endpoint was used, because various exploratory analyses were performed. |
| Percentage of Participants With Adverse Events | 24 weeks | No primary endpoint was used, because various exploratory analyses were performed. |
| Percentage of Participants With Adverse Drug Reactions | 24 weeks | No primary endpoint was used, because various exploratory analyses were performed. |
| The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients | 24 weeks | No primary endpoint was used, because various exploratory analyses were performed. |
| Percentage of Participants With Abnormal Changes in Sensory Examinations | 24 weeks | No primary endpoint was used, because various exploratory analyses were performed. |
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-186 MCI-186 Injection 30 mg, 2 ampoules per treatment, once daily, intravenously infused over 60 min | 13 |
| Placebo of MCI-186 MCI-186 Injection Placebo, 2 ampoules per treatment, once daily, intravenously infused over 60 min | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | MCI-186 | Placebo of MCI-186 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 12 / 13 | 12 / 12 |
| serious Total, serious adverse events | 3 / 13 | 2 / 12 |
Outcome results
Primary
Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks
No primary endpoint was used, because various exploratory analyses were performed.
Time frame: baseline and 24 weeks
Population: 1 patient with missing value at baseline was excluded from the FAS in the 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 | -18.75 percentage of FVC | Standard Error 4.58 |
| Placebo of MCI-186 | Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | -15.69 percentage of FVC | Standard Error 4.58 |
Primary
Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks
No primary endpoint was used, because various exploratory analyses were performed. 0=worst; 48=best
Time frame: baseline and 24 weeks
| 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 | -6.52 units on a scale | Standard Error 1.78 |
| 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 units on a scale | Standard Error 1.83 |
Primary
Death or a Specified State of Disease Progression
No primary endpoint was used, because various exploratory analyses were performed. 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Death or a Specified State of Disease Progression | death | 1 events |
| MCI-186 | Death or a Specified State of Disease Progression | disability of independent ambulation | 4 events |
| MCI-186 | Death or a Specified State of Disease Progression | loss of upper arm function | 1 events |
| MCI-186 | Death or a Specified State of Disease Progression | tracheotomy | 0 events |
| MCI-186 | Death or a Specified State of Disease Progression | use of respirator | 0 events |
| MCI-186 | Death or a Specified State of Disease Progression | use of tube feeding | 1 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | use of respirator | 0 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | death | 0 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | tracheotomy | 0 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | disability of independent ambulation | 2 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | use of tube feeding | 0 events |
| Placebo of MCI-186 | Death or a Specified State of Disease Progression | loss of upper arm function | 2 events |
Primary
Percentage of Participants With Abnormal Changes in Sensory Examinations
No primary endpoint was used, because various exploratory analyses were performed.
Time frame: 24 weeks
Population: A note:~Each three patients of both groups did not have data to Staggering due to data missing. Therefore, concerning staggering, the number of participants analysed are 10 in the MCI-186 group and 9 in the placebo of MCI-186 group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Numbness | 0 percentage of participants |
| MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 10 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 | 0 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Staggering | 0 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Abnormal Changes in Sensory Examinations | Vibratory sensation | 0 percentage of participants |
Primary
Percentage of Participants With Adverse Drug Reactions
No primary endpoint was used, because various exploratory analyses were performed.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 | Percentage of Participants With Adverse Drug Reactions | 23.1 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Drug Reactions | 8.3 percentage of participants |
Primary
Percentage of Participants With Adverse Events
No primary endpoint was used, because various exploratory analyses were performed.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MCI-186 | Percentage of Participants With Adverse Events | 92.3 percentage of participants |
| Placebo of MCI-186 | Percentage of Participants With Adverse Events | 100 percentage of participants |
Primary
The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients
No primary endpoint was used, because various exploratory analyses were performed.
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MCI-186 | The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients | White blood cell count (WBC) | 23.1 percentage of participants |
| MCI-186 | The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients | Other laboratory tests except for WBC | 0 percentage of participants |
| Placebo of MCI-186 | The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients | White blood cell count (WBC) | 8.3 percentage of participants |
| Placebo of MCI-186 | The Percentage of Participants With an Abnormal Change in Laboratory Tests That Occurred in More Than Two Patients | Other laboratory tests except for WBC | 0 percentage of participants |