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

NCT04326283 | Terminated Phase 1 DMC

• 1 other identifier: CT1SNR1611ALS1
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Lou Gehrig's disease

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of SNR1611: adverse events

  Observation of adverse events

  24-week (24-week extension and additional 48-week are optional)

Secondary Outcomes (5)

• K-ALSFRS-R score

  24-week (24-week extension and additional 48-week are optional)

• FVC

  24-week (24-week extension and additional 48-week are optional)

• CSF trough concentrations of SNR1611

  24-week (24-week extension and additional 48-week are optional)

• Plasma trough concentrations of SNR1611

  24-week (24-week extension and additional 48-week are optional)

• Milestone

  Additional 48-week (optional)

Study Arms (3)

Trametinib (0.5 mg)

EXPERIMENTAL

One tablet of trametinib 0.5 mg per day

Drug: Trametinib (0.5 mg)

Trametinib (1 mg)

EXPERIMENTAL

Two tablets of trametinib 0.5 mg per day

Drug: Trametinib (1 mg)

Riluzole (100 mg)

ACTIVE COMPARATOR

One tablet of riluzole 50 mg taken twice per day

Drug: Riluzole (100 mg)

Interventions

Trametinib (0.5 mg) DRUG

0.5 mg/day

Also known as: Meqsel, SNR1611

Trametinib (0.5 mg)

Trametinib (1 mg) DRUG

1 mg/day

Also known as: Meqsel, SNR1611

Trametinib (1 mg)

Riluzole (100 mg) DRUG

100 mg/day (50 mg twice)

Also known as: Yooritek

Riluzole (100 mg)

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genuv Inc.: lead

Study Sites (5)

Inje University Busan Paik Hospital

Busan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

trametinib; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Byoung Joon Kim

  Samsung Medical Center, Seoul, Republic of Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: K-ALSFRS-R score will be measured by independent outcome assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 30, 2020
• Study Start: April 2, 2020
• Primary Completion: April 28, 2023
• Study Completion: April 28, 2023
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5)