A randomized, double-blind, placebo-controlled, phase 2 study to assess safety, tolerability and efficacy of RT001 in patients with amyotrophic lateral sclerosis.

Abstract

RT001 is a deuterated synthetic homologue of linoleic acid, which makes membrane polyunsaturated fatty acids resistant to lipid peroxidation, a process involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We conducted a randomized, multicenter, placebo-controlled clinical trial. Patients with ALS were randomly allocated to receive either RT001 or placebo for 24 weeks. After the double-blind period, all patients received RT001 during an open-label phase for 24 weeks. The primary outcome measures were safety and tolerability. Key efficacy outcomes included the ALS functional rating scale (ALSFRS-R), %predicted slow vital capacity, and plasma neurofilament light chain concentration. In total, 43 patients (RT001=21; placebo=22) were randomized. RT001 was well tolerated; one patient required dose reduction due to adverse events (AEs). Numerically, there were more adverse events in the RT001 group compared to the placebo group (71% versus 55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a serious AE, though unrelated to treatment. The least-squares mean difference in ALSFRS-R total score at week 24 of treatment was 1.90 (95% CI: -1.39, 5.19) in favor of RT001, p = 0.25. The directions of other efficacy outcomes favored RT001 compared to placebo, although no inferential statistics were performed. Initial data indicate that RT001 is safe and well-tolerated. Given the exploratory nature of the study, a larger clinical trial is required to evaluate its efficacy.