A Phase 1 interventional study of AMX0114 and Placebo in ALS, sponsored by Amylyx Pharmaceuticals Inc.. Recruiting at 14 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-14.
Sponsored by Amylyx Pharmaceuticals Inc. · Phase 1, Interventional, and Treatment
This study is a placebo-controlled Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide (ASO) AMX0114 in adult participants with amyotrophic lateral sclerosis (ALS).
The purpose of this study is to determine how safe and tolerable the investigational drug, AMX0114, is for the treatment of amyotrophic lateral sclerosis (ALS).
AMX0114 is given by intrathecal injection, an injection in the lower back into the spinal canal, also known as lumbar puncture. This clinical trial is designed to test if the treatment is safe and tolerable by monitoring the incidence of adverse events, serious adverse events, dose limiting toxicities (DLTs), and incidence of abnormalities in clinical laboratory assessments, vital signs, physical and neurological examinations, and electrocardiograms (ECGs). This trial will also assess the effects of AMX0114 on biomarkers of ALS, including markers of neuronal death and neuroinflammation.
981 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 283 are open to participants now.
This study's planned enrollment of 48 is above the median of 36 across 667 interventional studies indexed under Amyotrophic Lateral Sclerosis.
Browse Amyotrophic Lateral Sclerosis studies →Amylyx Pharmaceuticals Inc. is the lead sponsor of 13 studies on the registry; 2 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 3 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
AMX0114 will be administered once every 4 weeks by intrathecal bolus injection for a total of up to 4 doses. Treatment will be administered on Day 1, followed by repeat dosing every 4 weeks at approximately Day 29, Day 57 and Day 85.
Drug: AMX0114
Placebo drug will be administered once every 4 weeks by intrathecal bolus injection for a total of up to 4 doses. Treatment will be administered on Day 1, followed by repeat dosing every 4 weeks at approximately Day 29, Day 57 and Day 85.
Other: Placebo
Antisense oligonucleotides (ASOs) are a type of medicine that treats diseases by intercepting the mRNA messages sent within the cell, resulting in fewer specific proteins being made. AMX0114 is an ASO that targets the mRNA messenger that instructs the body to create a protein called calpain-2. Calpain-2 has been linked to the degeneration and death of neurons in many neurological diseases, including people living with sporadic ALS. AMX0114 is designed to reduce the levels of calpain-2, with the goal of slowing down the process that leads to neuron injury and death.
Placebo
Evaluate the safety and tolerability of AMX0114 in adult participants living with ALS
Incidence of adverse events (AEs), serious adverse events (SAEs) and dose limiting toxicities (DLTs). Incidence of abnormalities in clinical laboratory assessments, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Time frame: Day 1 - Day 145 (End of Study)
Evaluate the PK of AMX0114
Evaluate PK concentrations, including plasma and CSF levels of AMX0114
Time frame: Day 1 - Day 145 (End of Study)
Change from baseline at dosing days and end of study in CSF calpain-2 levels.
Time frame: Day 1 - Day 145 (End of Study)
Change from baseline at dosing days and end of study in CSF and plasma NfL.
Time frame: Day 1 - Day 145 (End of Study)
Change from baseline at dosing days and end of study in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS - R).
The ALSFRS-R consists of 12 items across 4 subdomains of function (bulbar, fine motor, gross motor, and breathing) with each item scored on a scale from 0 (total loss of function) to 4 (no loss of function). Total scores range from 0 to 48, with higher scores indicating better function.
Time frame: Day 1 - Day 145 (End of Study)
Change from baseline at dosing days and end of study in Slow Vital Capacity (SVC).
Time frame: Day 1 - Day 145 (End of Study)
Plan to share: Yes — Proposals for access to IPD by qualified investigators will be reviewed by an independent review committee. Only the de-identified data elements needed to achieve the specific scientific aims of a proposal as outlined in a pre-specified analysis plan will be provided. Study documents such as protocol, SAP, ICF, and CSR, may be provided, if requested and if needed, to conduct the specified analyses.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
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Amyotrophic Lateral Sclerosis→
Amylyx Pharmaceuticals Inc.