A Study of LTX-002 in Adult Participants With Amyotrophic Lateral Sclerosis

A First-in-Human, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of Intrathecally Administered LTX-002 in Adult Participants With Amyotrophic Lateral Sclerosis

This study will examine what happens when patients with amyotrophic lateral sclerosis (ALS) are given an investigational medication (study drug) known as LTX-002. Specifically, the researchers will be looking at safety, tolerability (if someone has any side effects from the drug), pharmacokinetics (what the body does to the study drug) and pharmacodynamics (what the study drug does to the body). The study will also investigate the effect of the drug on indicators of the severity of ALS, such as markers in blood and in the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord, CSF) and on measures of the participant's ability to move, speak, and breathe.

Eligible participants will be asked to visit the study site 9 times and stay overnight once. In addition, there will be telephone or video calls with the study staff on 8 separate occasions. Procedures will include:

• A review of medical history and medications
• Physical exams, including a neurologic (nervous system) assessment
• Electrocardiograms (a measure of the heart's electrical activity)
• Blood, urine and cerebrospinal fluid (CSF) collection
• Measures of lung function
• Measures of speech
• Measures of muscle strength
• Scales to assess ALS symptoms and overall health, and feelings about suicide
• Administration of the study drug (or placebo) by injection into the CSF through a lumbar (lower spinal area) injection

Inclusion Criteria:

• Diagnosis of ALS per Gold Coast criteria
• ALS symptom onset less than 36 months prior to Screening
• Slow vital capacity ≥ 50% of predicted value
• Body mass index ≥18 and ≤40 kg/m2

Exclusion Criteria:

• Current evidence or history of a clinically significant medical condition that, in the Investigator's judgement, would impact the participant's safety, interpretation of study results, or place the participant at high risk of poor treatment compliance or of not completing the study
• History of brain or spinal abnormalities on magnetic imaging (MRI) or computed tomography (CT) that might interfere with the lumbar puncture (LP), cerebrospinal fluid (CSF) circulation or safety assessments
• Prior treatment with antisense oligonucleotide (ASO), small interfering RNA, stem cell therapy, or gene therapy for any indication
• Tracheostomy
• HIV, Hepatitis B or C infection (acute or chronic)
• Presence of implanted shunt (CSF) or vascular device
• Risk for uncontrolled bleeding
• Pregnant or breastfeeding