A phase III double-blind, placebo-controlled, randomized withdrawal trial of 5-aminolevulinic acid hydrochloride with sodium ferrous citrate for efficacy and safety in patients diagnosed as Leigh syndrome

Abstract Objective A phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP-004 (5-aminolevulinic acid hydrochloride and sodium ferrous citrate) in patients diagnosed as Leigh syndrome (LS) was conducted to confirm the efficacy and safety of SPP-004 in patients with LS showing central nervous system disorders. Methods Fifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients showing improved scores on the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) for cranial nervous symptoms and myopathy symptoms proceeded to a 48-week double-blind (DB) period, where they were randomized (1:1) to receive SPP-004 or placebo ( n =14 each). Efficacy was evaluated using NPMDS for the full analysis set (FAS) during the DB-period (SPP-004 n =13, Placebo n =14) and the entire study period ( n =54). Safety evaluation focused on adverse events (AEs) in all 54 patients administered SPP-004. Results The primary endpoint, the proportion of patients who discontinued due to inadequate efficacy at 48 weeks, was lower in the SPP-004 group (15.4% [95% CI: 1.9-45.4%]) compared to the placebo group (50.0% [23.0-77.0%]). Over 80% of the SPP-004 group maintained efficacy (p=0.0486). All adverse drug reactions were mild, with no notable differences in AEs between groups. Conclusion These findings suggest that SPP-004 is safe and may provide therapeutic effect for LS symptoms.