A phase 1 multiple ascending dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecally administered LY4256984 in participants with sporadic amyotrophic lateral sclerosis.

LY4256984 is an antisense oligonucleotide that affects the splicing of Unc-13 Homolog A (UNC13A) mRNA. In ALS, there is a loss of the TDP-43 protein in the cell nucleus, which leads to mis-splicing of Unc-13 Homolog A (UNC13A) mRNA. This treatment aims to correct this defect.

This phase 1 study is sponsored by Eli Lilly and aims to investigate the safety and tolerability of LY4256984 intrathecally (in the spinal fluid). Approximately 32 participants worldwide will be included in this study in 4 cohorts of 8 patients, in which 4 different doses of LY4256984 will be investigated. The randomisation ratio is 6:2 LY4256984 to placebo, and it will be administered four times over a period of approximately 3 months. The duration of the study is approximately 41 weeks.

Patients with ALS who are between 18 and 75 years of age, have had symptoms of ALS for less than 24 months and have a lung function (SVC) of ≥ 50% are eligible for this study.