Efficacy and Safety of 5-Aminolevulinic Acid Hydrochloride Combined with Sodium Ferrous Citrate in Pediatric Patients with Leigh Syndrome and Central Nervous System Disorders: An Initial Exploratory Trial with a Double-Blind Placebo-Controlled Period, Followed by an Open-Label Period and a Subsequent Long-Term Administration Study.

An explorative study was conducted to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (SPP-004) in 10 pediatric patients with Leigh syndrome (LS) aged 3-24 months in 10 institutions between December 2014 and July 2019. The patients were randomized and allocated to the SPP-004 or placebo group for a 12-week double-blind period, followed by a 12-week open-label period with SPP-004 and then a long-term study of up to 180 weeks. The efficacy and safety were evaluated using the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) and adverse events (AEs), respectively. No significant differences were found between groups in NPMDS scores, but prolonged SPP-004 treatment stabilized or improved scores. During the initial double-blind phase, the serum lactate levels increased in the placebo group but not in the SPP-004 group. Over the period of prolonged treatment with SPP-004, the average serum lactate level gradually decreased to a normal level. One patient died due to heart failure, presumably due to an underlying disease. Overall, 7 out of 10 patients received SPP-004 without developing severe AEs until the termination of the long-term study. Given the severe symptoms and poor prognosis of pediatric LS, NPMDS scores were indicative of stabilization in pediatric LS patients treated with SPP-004.