Drug Discov Ther. 2025;19(6):404-413. (DOI: 10.5582/ddt.2025.01106)

A phase II investigator-initiated, continuation trial of 5-aminolevulinic acid hydrochloride/sodium ferrous citrate (5-ALA-HCl/SFC) for patients with adult-onset Still's disease (AOSD) refractory to glucocorticoids

Sumiyoshi R, Koga T, Kamisawa O, Morimoto S, Hosogaya N, Yamamoto H, Hori M, Inaba Y, Hattori Y, Hikake T, Kurokawa T, Hanaoka H, Sato S, Migita K, Ogawa N, Hashimoto M, Kawakami A

The aim of this study is to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride/ sodium ferrous citrate (5-ALA-HCl/SFC) in patients with adult-onset Still's disease (AOSD) refractory to glucocorticoids during the maintenance treatment period of a phase II investigator-initiated randomized, double-blind, parallel-group clinical trial. This multicenter, open-label, continuous trial was limited to participants from the preceding study, which was planned for 30 enrollees but was stopped early after four enrollees because of slow recruitment. The current trial maintained a 16-week treatment period and remained double-blind until the previous study database was locked and unblinded. Two dose groups were used: 5-ALA-HCl/SFC 100 and 300 mg. Participants previously assigned to placebo were re-randomized 1:1 to either dose group. The dosage and administration were identical to those of the previous protocol. The primary endpoint was the achievement of adapted ACR 30 at week 16. All four participants achieved the primary endpoints. Secondary outcomes, including the adapted ACR 90/100 and the change in serum ferritin levels, showed numerically greater improvement in the participant who received the high-dose compared with the other. Eleven adverse events occurred in three participants, including one serious event and one discontinuation; all were deemed unrelated to the study drug, and no deaths were reported. This study identified potential efficacy signals, particularly in the high-dose group. However, because of premature termination and a very limited sample size, the data were insufficient to establish the efficacy and safety profile of 5-ALA-HCl/SFC in refractory AOSD. Larger studies are required to confirm these findings.

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