Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Lou Gehrig's disease
Brief summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of trametinib (SNR1611) in the treatment of amyotrophic lateral sclerosis.
Detailed description
Trametinib (SNR1611) is a MEK inhibitor that downregulates the MAPK/ERK pathway. In this study, the potential of MAPK/ERK pathway downregulation through trametinib (SNR1611) as a therapeutic treatment for amyotrophic lateral sclerosis (ALS) will be evaluated.
Interventions
DRUGTrametinib (0.5 mg)
0.5 mg/day
DRUGTrametinib (1 mg)
1 mg/day
100 mg/day (50 mg twice)
Sponsors
Genuv Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
K-ALSFRS-R score will be measured by independent outcome assessors.
Intervention model description
Patients will be randomly assigned 4:1 to receive SNR1611 (0.5, 1 mg) or riluzole as an active comparator. The study will initiate with the first group of patients who will receive SNR1611 (0.5 mg, 8 patients) or riluzole (100 mg, 2 patients), while the initiation of the next dose groups will be decided by the IDMC (Independent Data Monitoring Committee) through safety assessment of the first 4-week periods of prior dose groups.
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion criteria: * Patients diagnosed as definite, probable or probable-laboratory-supported ALS according to El Escorial Criteria. * Patients of less than 2 years after the onset of ALS. * Patients who meet the criteria of K-ALSFRS-R score and forced vital capacity. Main
Exclusion criteria
* Patients with primary lateral sclerosis, progressive muscular atrophy or lower motor neuron disease. * Patients who have history of ALS treatment of edaravone or stem cell therapy within 16 weeks before screening. * Patients who have permanently ceased the administration of riluzole due to lack of tolerability and/or efficacy. * Patients in Class II to IV according to the New York Heart Association functional classification. Patients with myocardial infarction, unstable arrhythmia, and/or significant cardiovascular disease such as unstable angina within 12 weeks before screening. * Patients who do not meet the criteria of laboratory tests and medical/operation history.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of SNR1611: adverse events | 24-week (24-week extension and additional 48-week are optional) | Observation of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| K-ALSFRS-R score | 24-week (24-week extension and additional 48-week are optional) | Change in Korean Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (K-ALSFRS-R) score from baseline |
| FVC | 24-week (24-week extension and additional 48-week are optional) | Change in Forced Vital Capacity (FVC) from baseline |
| CSF trough concentrations of SNR1611 | 24-week (24-week extension and additional 48-week are optional) | Trough concentrations of SNR1611 in cerebrospinal fluid (CSF) |
| Plasma trough concentrations of SNR1611 | 24-week (24-week extension and additional 48-week are optional) | Trough concentrations of SNR1611 in plasma |
| Milestone | Additional 48-week (optional) | Time to event milestones |
Countries
South Korea
Outcome results
None listed