A Study of LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

A Multiple Ascending Dose Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

The purpose of this study is to evaluate how well LY4256984 is tolerated and what side effects may occur in participants with sporadic amyotrophic lateral sclerosis (ALS). The study drug will be administered intrathecally (IT) into the spine. Blood tests will be performed to check how much LY4256984 gets into the bloodstream and how long it takes the body to eliminate it.

Inclusion Criteria:

• Have a definite, possible, or probable diagnosis of sporadic amyotrophic lateral sclerosis (ALS) made by a physician experienced with the management of ALS
• ALS symptom onset as determined by the Investigator within 24 months of Screening
• Have a body mass index (BMI) within the range of greater than or equal to 18.0 and less than or equal to 35.0 kilogram per square meter (kg/m²) (inclusive)

Exclusion Criteria:

• Have a history or presence of medical illness including, but not limited to, any cardiovascular, renal, hepatic, gastrointestinal, respiratory, hematological, endocrine, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality
• Have a history of another neurodegenerative disease or significant dementia/severe cognitive problems
• Have serum alanine aminotransferase (ALT), aspartate transferase (AST), or total bilirubin levels greater than 2 x upper limit of normal.
• Have a significant renal impairment (estimated glomerular filtration rate <60 milliliters per minute [mL/min]/1.73 m²).
• Have a 12-lead electrocardiogram (ECG) abnormality at screening, in the opinion of the investigator, that increases the risks associated with participating in the study
• Show clinically significant abnormalities in lumbar spine previously known or determined by screening lumbar X-ray or fluoroscopy (if performed)