AMX0114 for ALS

(LUMINA Trial)

Recruiting at 15 trial locations

Overseen By Medical Director, Amylyx

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amylyx Pharmaceuticals Inc.

Must be taking: Riluzole, Edaravone

Must not be taking: ASO, Gene therapy

Disqualifiers: Tracheostomy, Liver dysfunction, others

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMX0114 for individuals with amyotrophic lateral sclerosis (ALS), a disease affecting nerve cells in the brain and spinal cord. The study aims to determine if AMX0114 is safe and well-tolerated when administered every four weeks, compared to a placebo (a substance with no therapeutic effect). Participants should have received an ALS diagnosis within the last two years and may be on stable doses of other ALS treatments like riluzole. Those experiencing frequent muscle weakness and managing ALS for less than two years might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how AMX0114 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on riluzole or edaravone, you must have been on a stable dose for at least 30 days before starting the study and continue it throughout the trial.

Is there any evidence suggesting that AMX0114 is likely to be safe for humans?

Research has shown that AMX0114 has been safe in animal studies, marking a crucial first step before human testing. This early study primarily assesses the treatment's safety for humans and monitors any side effects.

Limited information from human tests means early trials like this one are essential for gathering safety data before progressing to larger studies. So far, reports have not indicated any serious side effects from AMX0114. For those considering joining this trial, initial tests suggest AMX0114 has been safe, but this study will further confirm its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for ALS, such as riluzole and edaravone, aim to slow disease progression, but AMX0114 offers a novel approach. Unlike these standard options, AMX0114 is administered through an intrathecal bolus injection directly into the spinal fluid, targeting the nervous system more directly. This delivery method could potentially enhance the drug’s effectiveness by ensuring it reaches the central nervous system more efficiently. Researchers are excited about AMX0114 because it represents a new mechanism of action that might better address the underlying disease processes of ALS, offering hope for improved outcomes.

What evidence suggests that AMX0114 might be an effective treatment for ALS?

Research has shown that AMX0114, which participants in this trial may receive, has shown promising results in early studies for ALS (amyotrophic lateral sclerosis). In lab tests, AMX0114 reduced a specific RNA linked to nerve cell damage by over 99%, suggesting it might help slow nerve damage in ALS. Animal studies showed the drug was well-tolerated, indicating potential safety for humans. These early findings suggest that AMX0114 could effectively treat ALS. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director, Amylyx

Principal Investigator

Medical Monitor

Are You a Good Fit for This Trial?

Adults diagnosed with ALS within the last 24 months can join this trial. They must understand the study, agree to follow its rules, and give informed consent. Women who could get pregnant and men must use birth control during the trial and for some time after. Participants already on certain ALS medications need a stable dose for at least 30 days before starting.

Inclusion Criteria

I have been on a stable dose of riluzole and/or edaravone for at least 30 days.

I understand the study's risks and agree to follow its requirements.

I have been diagnosed with ALS by an experienced doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMX0114 or placebo by intrathecal injection every 4 weeks for up to 4 doses

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AMX0114

Trial Overview The trial is testing AMX0114 against a placebo in people with ALS. It's a Phase I study focusing on how safe it is, how well it's tolerated, what happens to it in the body (pharmacokinetics), and what effects it has (pharmacodynamics).

How Is the Trial Designed?

Group I: Active Treatment: AMX0114 Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Amylyx Pharmaceuticals Inc.

Lead Sponsor

Trials

12

Recruited

1,600+

Published Research Related to This Trial

About 10% of amyotrophic lateral sclerosis (ALS) cases are familial, with most mutations found in the SOD1 gene, particularly the A4V mutation, which leads to a severe and rapid disease progression.

Presymptomatic testing for familial ALS is challenging due to uncertainty about the mutation's responsibility for the disease and its age of onset, highlighting the need for careful genetic counseling similar to that used in Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Where is the role of the genetic investigations in amyotrophic lateral sclerosis?]. Vandenberghe, N.[2009]

A specific mutation (A4V) in the SOD1 gene was identified in a 51-year-old Chinese male with familial amyotrophic lateral sclerosis (ALS), marking the first report of this mutation in a non-Caucasian patient.

The patient exhibited a typical A4V-related ALS phenotype, characterized by rapid disease progression and significant lower motor neuron involvement, indicating that this mutation has similar effects across different ethnic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an A4V SOD1 mutation in a Chinese patient with amyotrophic lateral sclerosis without the A4V founder effect common in North America. Tang, L., Ma, Y., Liu, X., et al.[2022]

The Angiogenin (ANG) K17I variant is found to be rare in Caucasian populations, with frequencies of 0.43% in ALS patients and 0.16% in controls, suggesting it is not a common risk factor for the disease.

However, the K17I variant is associated with an increased risk of amyotrophic lateral sclerosis (ALS), particularly familial ALS (FALS), with odds ratios indicating a significant risk, while no such association was found for sporadic ALS (SALS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between the Angiogenin (ANG) K17I variant and amyotrophic lateral sclerosis risk in Caucasian: a meta-analysis. Pan, L., Deng, X., Ding, D., et al.[2022]

A novel mutation in the Angiogenin gene (ANG) was identified in a sporadic ALS patient from southern Italy, suggesting a potential genetic link to the disease.

The study also found an association between the ANG gene and a specific single nucleotide polymorphism (rs11701) in familial ALS cases, reinforcing the gene's involvement in ALS pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy. Conforti, FL., Sprovieri, T., Mazzei, R., et al.[2011]

The phase 2 trial of AMX0035 demonstrated statistically significant effects in slowing ALS progression in a small sample of 137 patients, with a p-value of 3%, indicating potential efficacy.

Using Bayesian decision analysis, the optimal type I error rate for FDA approval of AMX0035 could be higher than the initial 3% if the therapy is at least 30% likely to be effective, suggesting a flexible approach to evaluating its approval based on patient needs and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating patient preferences and burden-of-disease in evaluating ALS drug candidate AMX0035: a Bayesian decision analysis perspective. Xu, Q., Cho, J., Ben Chaouch, Z., et al.[2023]

The Accurate Test of Limb Isometric Strength (ATLIS) was found to be more sensitive to changes in strength in ALS patients compared to the ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC), making it a better measure for tracking disease progression.

Using ATLIS could potentially reduce the sample size needed for clinical trials by about one-third, which is significant for early trials aiming to detect subtle changes in muscle strength before functional decline occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed dynamometry is more sensitive than vital capacity or ALS rating scale. Andres, PL., Allred, MP., Stephens, HE., et al.[2017]

Recent clinical trials in amyotrophic lateral sclerosis (ALS) have successfully enrolled more homogeneous patient populations by using specific inclusion criteria, leading to observed efficacy signals in smaller and shorter studies than previously thought possible.

While the ALS Functional Rating Scale-Revised remains the primary outcome measure, blood neurofilament levels show promise as a prognostic indicator, although they are not yet validated for use as a primary outcome in trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyotrophic Lateral Sclerosis Clinical Trials and Interpretation of Functional End Points and Fluid Biomarkers: A Review. Shefner, JM., Bedlack, R., Andrews, JA., et al.[2023]

ALS is a complex neurodegenerative disease with no effective therapy currently available, but early diagnosis and risk prediction using proteomic biomarkers and microRNAs could help identify individuals at risk before symptoms develop.

Gene therapies, such as antisense oligonucleotides, have shown promise in treating other neurodegenerative diseases and may offer hope for developing effective treatments for ALS in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies of Genetic and Proteomic Risk Factors of Amyotrophic Lateral Sclerosis Inspire Biomarker Development and Gene Therapy. Bagyinszky, E., Hulme, J., An, SSA.[2023]

Despite two completed clinical trials for ALS yielding negative results, the identification of new ALS-associated genes offers hope for future research and potential treatments.

The discovery of biomarkers in body fluids and imaging techniques suggests progress in understanding ALS, which may lead to improved diagnostic and therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor neuron disease in 2014. Biomarkers for ALS--in search of the Promised Land. Chiò, A., Traynor, BJ.[2019]

Long-term mechanical ventilation significantly prolongs survival in patients with amyotrophic lateral sclerosis (ALS), with those receiving invasive ventilation showing a mean survival of 72 months.

Programmed pulmonary assessment before initiating non-invasive ventilation (NIV) positively impacts survival rates, highlighting the importance of a multidisciplinary approach in managing ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyotrophic lateral sclerosis: impact of pulmonary follow-up and mechanical ventilation on survival. A study of 114 cases. Sanjuán-López, P., Valiño-López, P., Ricoy-Gabaldón, J., et al.[2022]

Citations

1. amylyx.com amylyx.com/news/amylyx-pharmaceuticals-receives-us-fda-fast-track-designation-for-amx0114-for-the-treatment-of-amyotrophic-lateral-sclerosis

Amylyx Pharmaceuticals Receives U.S. FDA Fast Track ... AMX0114 was well-tolerated in in vivo preclinical safety studies. About ALS. Amyotrophic lateral sclerosis (ALS, also known as motor neuron ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06665165

AMX0114 in Adult Participants With Amyotrophic Lateral ... The purpose of this study is to determine how safe and tolerable the investigational drug, AMX0114, is for the treatment of amyotrophic lateral sclerosis ...

3. alsnetwork.org alsnetwork.org/first-patient-dosed-in-a-phase-1-study-testing-amx0114-in-als/

First Patient Dosed in a Phase 1 Study Testing AMX0114 ... Each participant will receive up to four doses, given once a month. For every person receiving a placebo, three will receive the therapy, which ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/amylyx-therapy-trial/

First subject dosed in Amylyx's Phase I trial of ALS therapy Amylyx Pharmaceuticals has dosed the first subject in the Phase I LUMINA trial, investigating AMX0114, a potential treatment for ALS.

5. mdaconference.org mdaconference.org/abstract-library/development-and-preclinical-assessment-of-amx0114-an-antisense-oligonucleotide-targeting-calpain-2-a-critical-effector-of-axonal-degeneration/

Development and Preclinical Assessment of AMX0114 In the human motor neuron cell line, AMX0114 reduced CAPN2 RNA levels by ≥99%; the potency (half maximal effective concentration, EC50) was ~40 nM. Treatment ...

6. amylyx.com amylyx.com/document/NEALS-LUMINA.pdf

NEALS-LUMINA.pdf Ascending Dose Study to Evaluate the Safety and Tolerability of. AMX0114 in Amyotrophic Lateral Sclerosis (LUMINA). Lauren Kett,1 Sabrina ...

7. neurologyadvisor.com neurologyadvisor.com/news/calpain-2-targeting-antisense-oligonucleotide-fast-tracked-for-als/

Calpain-2 Targeting Antisense Oligonucleotide Fast ... AMX0114 is an investigational antisense oligonucleotide targeting calpain-2 (CAPN2), a calcium-activated protease believed to play a role in ALS disease ...