{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:05:40Z","timestamp":1784311540088,"version":"3.55.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP\u2011004 (5\u2011aminolevulinic acid hydrochloride and sodium ferrous citrate) was conducted to confirm the efficacy and safety of SPP-004 for maintenance of clinical response in patients diagnosed with Leigh syndrome (LS) showing central nervous system disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients who showed improvement 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\u2011004 or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914 each). Efficacy was evaluated using NPMDS for the full analysis set (FAS) during the DB\u2011period (SPP-004\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913, Placebo\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914) and the entire study period (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200954). Safety evaluation focused on adverse events (AEs) in all 54 patients administered SPP-004.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u201345.4%]) compared to the placebo group (50.0% [23.0\u201377.0%]). Over 80% of the SPP-004 group showed maintained efficacy (p\u2009=\u20090.0486). All adverse drug reactions were mild, with no notable differences in AEs between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that SPP-004 is safe and may provide therapeutic effect for LS patients who achieved an initial clinical response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0332283","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:51:32Z","timestamp":1784310692000},"page":"e0332283","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase III double-blind, placebo-controlled, randomized withdrawal trial of 5\u2011aminolevulinic acid hydrochloride with sodium ferrous citrate for efficacy and safety in patients diagnosed as Leigh 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