Clinical trial NCT06665165: AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: ALS
Keywords: Amyotrophic Lateral Sclerosis
Sporadic ALS
Motor Neuron Disease
Antisense oligonucleotide
ASO
Calpain-2
Lead sponsor: Amylyx Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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 75%.
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.

Primary outcomes:
measure: Evaluate the safety and tolerability of AMX0114 in adult participants living with ALS
timeFrame: Day 1 - Day 145 (End of Study)
Secondary outcomes:
measure: Evaluate the PK of AMX0114
timeFrame: Day 1 - Day 145 (End of Study)
Other outcomes:
measure: Change from baseline at dosing days and end of study in CSF calpain-2 levels.
timeFrame: Day 1 - Day 145 (End of Study)
measure: Change from baseline at dosing days and end of study in CSF and plasma NfL.
timeFrame: Day 1 - Day 145 (End of Study)
measure: Change from baseline at dosing days and end of study in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS - R).
timeFrame: Day 1 - Day 145 (End of Study)
measure: Change from baseline at dosing days and end of study in Slow Vital Capacity (SVC).
timeFrame: Day 1 - Day 145 (End of Study)
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital Pasquerilla Healthcare Center
state: District of Columbia
city: Boston
country: United States
facility: Massachusetts General Hospital, Healey & AMG Center for ALS
state: Massachusetts
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
Study officials:
affiliation: Medical Monitor
name: Medical Director, Amylyx
role: STUDY_DIRECTOR
References: