Clinical trial NCT04326283: Trial of Safety, Tolerability and Efficacy of Trametinib (SNR1611) in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official title: A Sequential Dose-Escalation, Randomized, Active-Controlled, Multi-Center, Phase 1/2a Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of SNR1611 in Patients With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lou Gehrig's disease
Lead sponsor: Genuv Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-30
Enrollment: 23
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Safety and tolerability of SNR1611: adverse events
timeFrame: 24-week (24-week extension and additional 48-week are optional)
Secondary outcomes:
measure: K-ALSFRS-R score
timeFrame: 24-week (24-week extension and additional 48-week are optional)
measure: FVC
timeFrame: 24-week (24-week extension and additional 48-week are optional)
measure: CSF trough concentrations of SNR1611
timeFrame: 24-week (24-week extension and additional 48-week are optional)
measure: Plasma trough concentrations of SNR1611
timeFrame: 24-week (24-week extension and additional 48-week are optional)
measure: Milestone
timeFrame: Additional 48-week (optional)
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
Study officials:
affiliation: Samsung Medical Center, Seoul, Republic of Korea
name: Byoung Joon Kim
role: PRINCIPAL_INVESTIGATOR
References: