AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis (LUMINA)

April 9, 2026 updated by: Amylyx Pharmaceuticals Inc.

Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate Safety, Tolerability, PK and PD of Antisense Oligonucleotide AMX0114 Administered to Adult Participants With Amyotrophic Lateral Sclerosis

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • Recruiting
        • University of Calgary
        • Principal Investigator:
          • Collin Luk, MD, PhD
        • Contact:
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Recruiting
        • McMaster University
        • Contact:
        • Principal Investigator:
          • Marvin Chum, MD
      • London, Ontario, Canada, N6G 2M3
        • Recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Christen Shoesmith, MD
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • McGill University Health Centre - Centre for Innovative Medicine
        • Principal Investigator:
          • Angela Genge, MD
        • Contact:
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University of California, San Diego
        • Principal Investigator:
          • John Ravits, MD
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University Hospital Pasquerilla Healthcare Center
        • Principal Investigator:
          • Shakti Nayar, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32611
        • Recruiting
        • University of Florida
        • Principal Investigator:
          • James Wymer, MD, FAAN
        • Contact:
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic in Florida
        • Principal Investigator:
          • Bjorn Oskarsson, MD
        • Contact:
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Regional Medical Center, Orlando Health Neuroscience Institute
        • Contact:
        • Principal Investigator:
          • Vahid Tohidi, MD, PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital, Healey & AMG Center for ALS
        • Principal Investigator:
          • Sabrina Paganoni, MD, PhD
        • Contact:
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Eric Sorenson, MD
        • Contact:
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
    • Tennessee
    • Texas
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Ability to understand the purpose and risks of this study, willingness to comply with the study and to provide informed consent in accordance with local laws and regulations.
  2. Male or female, at least 18 years of age.
  3. Diagnosis of clinically definite or clinically probable ALS, made by a physician who is experienced with management of ALS.
  4. Time since onset of first symptom of ALS should be <24 months prior to beginning the study. Date of ALS symptom onset is defined as the onset of weakness (in the limbs, bulbar region, or trunk).
  5. If the participant is to be treated with riluzole and/or edaravone before or during the trial, then treatment must be previously started and maintained at a stable regimen for at least 30 days prior to starting the study and through the end of the study.
  6. Women of childbearing potential (e.g., not post-menopausal for at least one year or surgically sterile) must agree to use an acceptable birth control method for the duration of the trial and 60 days after the last dose of Study Drug or be of non-childbearing potential.
  7. Female participants or female partners of male participants must not be pregnant or plan to become pregnant for the duration of the trial and for up to 90 days after the last dose of Study Drug.
  8. Male participants must agree to abstain from sperm donation for the duration of the trial and practice contraception with a female partner, for at least 90 days after last dose of Study Drug.

Exclusion Criteria:

  1. Presence of tracheostomy or permanent assisted ventilation.
  2. SVC less than 65%.
  3. Abnormal liver function defined as aspartate aminotransferase and/or alanine aminotransferase > 3 times the upper limit of normal (ULN) and/or total bilirubin > 1.5 times the ULN (obtained within 4 weeks of first dose) except when a result of Gilbert syndrome.
  4. Abnormal renal function defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
  5. Other laboratory abnormalities, including abnormalities in platelet count, international normalized ratio, prothrombin time, and activated partial thromboplastin time.
  6. Pregnant women (confirmed by a pregnancy test within 7 days prior to first dose) or women currently breastfeeding.
  7. Current or previous clinically significant, unstable medical condition (other than ALS), that in the opinion of the Investigator could affect a participant's safety or ability to comply with the study.
  8. Significant abnormalities in physical/neurological examination, vital signs, or electrocardiogram (ECG), which in the opinion of the Investigator could affect the safety of the participant.
  9. Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that could affect the participant's ability to provide informed consent or comply with study procedures.
  10. Current or previous enrollment in another trial involving use of an investigational therapy, in most cases within 30 days after the last dose of the study drug, prior to starting this study.
  11. Current or previous treatment with small interfering ribonucleic acid, stem cell therapy, any ASO or gene therapy.
  12. Any contraindications for lumbar puncture or repeated intrathecal injection and/or underlying disorders that could be affected by intrathecal injections.
  13. Prior severe reaction or known hypersensitivity to any part of the Study Drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active Treatment: AMX0114
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
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 Comparator: Placebo
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
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety and tolerability of AMX0114 in adult participants living with ALS
Time Frame: Day 1 - Day 145 (End of Study)

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).
Day 1 - Day 145 (End of Study)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the PK of AMX0114
Time Frame: Day 1 - Day 145 (End of Study)
Evaluate PK concentrations, including plasma and CSF levels of AMX0114
Day 1 - Day 145 (End of Study)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline at dosing days and end of study in CSF and plasma NfL.
Time Frame: Day 1 - Day 145 (End of Study)
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)
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).
Time Frame: Day 1 - Day 145 (End of Study)
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.
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)
Day 1 - Day 145 (End of Study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amylyx Pharmaceuticals Inc.

Investigators

  • Study Director: Medical Director, Amylyx, Medical Monitor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2025

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

October 25, 2024

First Submitted That Met QC Criteria

October 28, 2024

First Posted (Actual)

October 30, 2024

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A114-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

TBD: proposals for access to IPD will be reviewed after data is used in regulatory approval in all major countries or regions where filing is planned or after publication, whichever is latest. Exact timing is not currently known.

IPD Sharing Access Criteria

Access to IPD will be granted to qualified investigators whose proposed use of the data has been approved by an independent review committee to achieve the aims in their proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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