AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis

NCT06665165 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: A114-001
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 14

Brief Summary

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).

Conditions

ALS

Keywords

Amyotrophic Lateral Sclerosis; Sporadic ALS; Motor Neuron Disease; Antisense oligonucleotide; ASO; Calpain-2

Outcome Measures

Primary Outcomes (1)

• 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).

  Day 1 - Day 145 (End of Study)

Secondary Outcomes (1)

• Evaluate the PK of AMX0114

  Day 1 - Day 145 (End of Study)

Other Outcomes (4)

• Change from baseline at dosing days and end of study in CSF calpain-2 levels.

  Day 1 - Day 145 (End of Study)

• Change from baseline at dosing days and end of study in CSF and plasma NfL.

  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).

  Day 1 - Day 145 (End of Study)

Study Arms (2)

Active Treatment: AMX0114

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Interventions

AMX0114 DRUG

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.

Active Treatment: AMX0114

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• Male or female, at least 18 years of age.
• Diagnosis of clinically definite or clinically probable ALS, made by a physician who is experienced with management of ALS.
• 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).
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Presence of tracheostomy or permanent assisted ventilation.
• SVC less than 65%.
• 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.
• Abnormal renal function defined as estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2.
• Other laboratory abnormalities, including abnormalities in platelet count, international normalized ratio, prothrombin time, and activated partial thromboplastin time.
• Pregnant women (confirmed by a pregnancy test within 7 days prior to first dose) or women currently breastfeeding.
• 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.
• 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.
• 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.
• 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.
• Current or previous treatment with small interfering ribonucleic acid, stem cell therapy, any ASO or gene therapy.
• Any contraindications for lumbar puncture or repeated intrathecal injection and/or underlying disorders that could be affected by intrathecal injections.
• Prior severe reaction or known hypersensitivity to any part of the Study Drug.

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead

Study Sites (14)

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

Georgetown University Hospital Pasquerilla Healthcare Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Florida

Gainesville, Florida, 32611, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Orlando Regional Medical Center, Orlando Health Neuroscience Institute

Orlando, Florida, 32806, United States

RECRUITING

Massachusetts General Hospital, Healey & AMG Center for ALS

Boston, Massachusetts, 02114, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Temple University of the Commonwealth System of Higher Education

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37909, United States

RECRUITING

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

RECRUITING

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

RECRUITING

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6G 2M3, Canada

RECRUITING

McGill University Health Centre - Centre for Innovative Medicine

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director, Amylyx

  Medical Monitor

  STUDY DIRECTOR

Central Study Contacts

Medical Director, Amylyx

CONTACT

857-320-6200; clinicaltrials@amylyx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 30, 2024
• Study Start: April 7, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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.

Locations

CA (4); US (10)