ALSPhase 1LUMINANCT06665165
AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis
A Phase 1 study testing AMX0114 in people with ALS, run by Amylyx Pharmaceuticals Inc. at 14 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALS
- What is being tested?
- AMX0114
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 7 Apr 2025to Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
14 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 2 countries
United States10 sites, 10 recruiting
- Recruiting
Massachusetts General Hospital, Healey & AMG Center for ALS
Boston, Massachusetts, 02114
Lucy Lee, 617-643-7434, amx0114healey@mgb.org
Anika Allen, 617-724-9196, amx0114healey@mgb.org
- Recruiting
University of Florida
Gainesville, Florida, 32611
Jennifer Steshyn, 518-262-5226, jennifer.steshyn@neurology.ufl.edu
James Wymer, MD, FAAN
- Recruiting
Houston Methodist Neurological Institute
Houston, Texas, 77030
Jennifer Garrett, 634-238-4516, jmgarrett@houstonmethodist.org
Madison Taylor, 346-356-3678, mtaylor5@houstonmethodist.org
- Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Jeffery Gainer, 904-244-4693, jeffery.gainer@jax.ufl.edu
Bjorn Oskarsson, MD
- Recruiting
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, 37909
Patricia Pryor, 865-305-9100, patricia.pryor@amr-clinical.com
Felicia Hiatt, Felicia.Hiatt@amr-clinical.com
- Recruiting
University of California, San Diego
La Jolla, California, 92093
Rose Previte, 858-246-1319, rprevite@ucsd.edu
John Ravits, MD
- Recruiting
Orlando Regional Medical Center, Orlando Health Neuroscience Institute
Orlando, Florida, 32806
Charlene Carlo, 321-841-1324, Charlene.carlo@orlandohealth.com
Vahid Tohidi, MD, PhD
- Recruiting
Temple University of the Commonwealth System of Higher Education
Philadelphia, Pennsylvania, 19140
Kathleen Hatala, 215-707-4171, kathleen.hatala@tuhs.temple.edu
Christine Barr, 215-707-5440, christine.barr@tuhs.temple.edu
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Brenda Nelson, 507-293-9237, nelson.brenda6@mayo.edu
Jeff Laivell, 507-538-8095, laivell.jeffrey@mayo.com
- Recruiting
Georgetown University Hospital Pasquerilla Healthcare Center
Washington D.C., District of Columbia, 20007
Cate Ledoux, 240-681-9556, csl83@georgetown.edu
Shakti Nayar, MD
Canada4 sites, 4 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 4Z6
Janet Petrillo Ballantyne, 403-210-7006, japetril@ucalgary.ca
Collin Luk, MD, PhD
- Recruiting
McMaster University
Hamilton, Ontario, L8N 3Z5
Daniela Trapsa, 905-521-2100 ext. 76368, trapsd@mcmaster.ca
Marvin Chum, MD
- Recruiting
London Health Sciences Centre
London, Ontario, N6G 2M3
Denise Hulley, 5196858500 ext. 34345, denise.hulley@lhsc.on.ca
Christen Shoesmith, MD
- Recruiting
McGill University Health Centre - Centre for Innovative Medicine
Montreal, Quebec, H4A 3J1
Maria Gobbo, maria.gobbo@muhc.mcgill.ca
Angela Genge, MD
About this study
Official title: 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).
Read the 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.
- Conditions
- ALS
- Being tested
- AMX0114, Placebo
- Keywords
- Amyotrophic Lateral Sclerosis, Sporadic ALS, Motor Neuron Disease, Antisense oligonucleotide, ASO, Calpain-2
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMX0114Drug
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.
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1 - Day 145 (End of Study)
Secondary outcomes (1)
Evaluate the PK of AMX0114
Evaluate PK concentrations, including plasma and CSF levels of AMX0114
Measured: Day 1 - Day 145 (End of Study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2024
- Study start7 Apr 2025
- Primary completionFeb 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amylyx Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Amylyx, Study director, Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06665165
- Sponsor's protocol ID
- A114-001
- Acronym
- LUMINA
- Status last verified
- Apr 2026
- First submitted
- 25 Oct 2024
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06665165
- Acronym / sponsor ID
- LUMINA / A114-001
- Conditions
- ALS
- Keywords
- Amyotrophic Lateral Sclerosis, Sporadic ALS, Motor Neuron Disease, Antisense oligonucleotide, ASO, Calpain-2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Amylyx Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 30 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Treatment: AMX0114 | Experimental | Drug: AMX0114AMX0114 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. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMX0114Antisense 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. | Drug | Active Treatment: AMX0114 |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
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).
1 secondary outcome
Evaluate the PK of AMX0114
Time frame: Day 1 - Day 145 (End of Study)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Director, Amylyx study director
Medical Monitor
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMX0114 in people with ALS, run by Amylyx Pharmaceuticals Inc. at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Director, Amylyx (857-320-6200, clinicaltrials@amylyx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of AMX0114 in adult participants living with ALS (time frame: Day 1 - Day 145 (End of Study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.