A multicentre, randomised, double-blind, placebo-controlled multiple ascending dose study to evaluate the safety and tolerability of QRL-201 in Amyotrophic Lateral Sclerosis.

QRL-201 is an antisense oligonucleotide that affects the splicing of the STMN2 gene. In ALS, a loss of the protein TDP-43 in the cell nucleus occurs and gives rise to mis-splicing of STMN2. This treatment aims to correct this defect.

This phase 1 study is sponsored by the Quralis Corporation and aims to assess the safety and tolerability of QRL-201 intrathecally (in the spinal fluid). This study will include approximately 64 participants worldwide in 8 cohorts of 8 patients, in which 6 different doses of QRL-201 will be investigated. The randomisation ratio is 6 : 2 QRL-201 to placebo and this will be administered five times over a time span of about 3 months. For patients in cohort 1-4, the study duration is about 36 weeks and for patients in cohort 5-8 it is about 20 weeks.

Patients with C9orf72 who are between 18 and 80 years old , have symptoms of ALS for less than 24 months and have a lung function (SVC) of ≥50% are eligible for this study.