Trial of Safety, Tolerability and Efficacy of Trametinib (SNR1611) in Patients With Amyotrophic Lateral Sclerosis (ALS)

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

The purpose of this study is to evaluate the safety, tolerability and efficacy of trametinib (SNR1611) in the treatment of amyotrophic lateral sclerosis.

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Trametinib (0.5 mg); Drug: Trametinib (1 mg); Drug: Riluzole (100 mg)

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Inho Seo; Phone Number: +82-2-542-0318; Email: info@genuv.com

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trametinib (0.5 mg); One tablet of trametinib 0.5 mg per day	Drug: Trametinib (0.5 mg); 0.5 mg/day; Other Names: Meqsel; SNR1611
Experimental: Trametinib (1 mg); Two tablets of trametinib 0.5 mg per day	Drug: Trametinib (1 mg); 1 mg/day; Other Names: Meqsel; SNR1611
Active Comparator: Riluzole (100 mg); One tablet of riluzole 50 mg taken twice per day	Drug: Riluzole (100 mg); 100 mg/day (50 mg twice); Other Names: Yooritek

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of SNR1611: adverse events	Observation of adverse events	24-week (24-week extension and additional 48-week are optional)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
K-ALSFRS-R score	Change in Korean Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (K-ALSFRS-R) score from baseline	24-week (24-week extension and additional 48-week are optional)
FVC	Change in Forced Vital Capacity (FVC) from baseline	24-week (24-week extension and additional 48-week are optional)
CSF trough concentrations of SNR1611	Trough concentrations of SNR1611 in cerebrospinal fluid (CSF)	24-week (24-week extension and additional 48-week are optional)
Plasma trough concentrations of SNR1611	Trough concentrations of SNR1611 in plasma	24-week (24-week extension and additional 48-week are optional)
Milestone	Time to event milestones	Additional 48-week (optional)

Collaborators and Investigators

• Sponsor: Genuv Inc.
• Investigators: Principal Investigator: Byoung Joon Kim, Samsung Medical Center, Seoul, Republic of Korea

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2020
• Primary Completion (Actual): April 28, 2023
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 27, 2020
• First Posted (Actual): March 30, 2020

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 7, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: ALS; Lou Gehrig's disease
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Protein Kinase Inhibitors; Anticonvulsants; Trametinib; Riluzole
• Other Study ID Numbers: CT1SNR1611ALS1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No