臨床研究等提出・公開システム

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 corticosteroids

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 corticosteroids

4

Four subjects were enrolled in this extension study following the initial study (NUH06AOSD). Of the four subjects, one subject who was in the placebo group in the initial study was enrolled in the low-dose group, so there was one subject in the high-dose group (HD) and three subjects in the low-dose group (LD). The age/gender of the four subjects were as follows: 77/female in HD, 54/male, 65/male, and 19/female in LD. Of the four subjects, three subjects had a history of treatment with drugs other than glucocorticoids, and one subject (placebo group in the initial study to LD) had no history of treatment with drugs other than glucocorticoids.

All four subjects who completed the prior study were enrolled in this study, with one in the high-dose group and three in the low-dose group. Of the three subjects in the low-dose group, two discontinued the administration of the study drug during the trial due to worsening of their primary disease on Day 37 and Day 71, respectively, but completed the remaining observation period of the trial after switching to standard treatment. All four subjects were included in the full analysis set.

Adverse events were observed in 3 out of 4 subjects (1 out of 1 subject in the high-dose group, 2 out of 3 subjects in the low-dose group), with a total of 11 events occurring (4 events in 1 subject in the high-dose group, 7 events in 2 subjects in the low-dose group). All adverse events were reported as not related to the study drug, and no side effects were observed. The severity of the adverse events was mild in 6 of 11 events, moderate in 4 events, and severe in 1 event. Outcomes were as follows: 9 out of 11 events resulted in recovery, and 2 events showed improvement. One serious adverse event (spinal compression fracture) and one adverse event (drug rash) leading to discontinuation of study drug administration were observed in the same subject (low-dose group); however, both adverse events were reported as not related to the study drug. There were no deaths, adverse events leading to death, or adverse events leading to study discontinuation.

The primary endpoint (Adapted ACR 30 response at 16-week) was met in all 4 subjects. Several secondary endpoints (e.g. Adapted ACR 90/100 response or change of baseline in serum ferritin levels) for the subject assigned to the high-dose group showed numerical improvement compared to those for the other three subjects.

Suggesting usefulness of some of the items for the subject assigned to the high-dose group was obtained. However, the collected data did not support the profile needed to clarify the efficacy and safety of the study drug due to the early termination of the clinical trial. Further investigation should be needed.

April. 01, 2025

June. 01, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071220086

Kawakami Atsushi

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan

tyosei_aosd@ml.nagasaki-u.ac.jp

Sumiyoshi Remi

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan

+81-95-819-8527

tyosei_aosd@ml.nagasaki-u.ac.jp

Complete

Jan. 07, 2023

Interventional

randomized controlled trial

open(masking not used)

dose comparison control

parallel assignment

treatment purpose

1) Patients who have completed 8 weeks of investigational drug administration in the prior study
2) Patients who are able to provide free and voluntary informed consent in writing and comply with the requirements of the study protocol. For subjects under 18 years of age, written consent must be obtained from a surrogate* and, in principle, from the patient him/herself.
*A person who has parental authority over the subject, spouse, guardian, or other equivalent person.
3) Female patients who can become pregnant or male patients who are sexually active with a female who can become pregnant who can obtain consent to use an effective contraceptive method (e.g., condom) during the study period and until the day after the last dose of the study drug.

1) Females who are lactating, pregnant, or intend to become pregnant during the study period
2) Patients with serious infectious diseases (including active tuberculosis)
3) Patients who have been off study medication for more than 14 consecutive days between the start of the prior study and the start of the continuation study
4) Patients who have been off study medication for more than 7 consecutive days from the week 8 evaluation date of the prior study to the time of enrollment
5) Patients who received a live vaccine between the end of the prior study and enrollment
6) Patients with porphyria/photohypersensitivity or a history of porphyria/photohypersensitivity
7) Patients with hemochromatosis
8) Patients with known allergy or hypersensitivity to, or intolerance to, aminolevulinic acid, sodium ferrous citrate, or their additives
9) Patients with macrophage activation syndrome (MAS) or disseminated intravascular coagulation syndrome since the start of the prior study
10) Patients on dialysis
11) Patients with severe hepatic dysfunction (either AST or ALT > 5 times the upper limit of the institutional reference value at the week 8 evaluation date of the prior study)
12) Patients who have used ALA-containing or iron-based drugs or supplements, biologic agents, molecular targeted therapies, or immunosuppressive drugs listed in 5.11. "Prohibited concomitant medications" between the completion of the prior study and enrollment
13) Patients who have started a new or increased dose of methotrexate or other disease-modifying anti-rheumatic drugs between the end of the prior study and the time of enrollment
14) Patients with serious complications that make them unsuitable for the study as determined by the investigator or subinvestigator.
15) Other patients deemed inappropriate by the investigator or subinvestigator.

Both

Adult Onset Still's Disease

Low dose group: 50 mg aminolevulinic acid and 39.2 mg sodium ferrous citrate orally twice daily
High dose group: 150 mg aminolevulinic acid and 117.6 mg sodium ferrous citrate orally twice daily

Adapted ACR 30 response at week 16 since administration of 5-ALA-HCl/SFC

Efficacy endpoints
1) Adapted ACR 30 response at week 4, 8, 12, 20, and 24 since administration of 5-ALA-HCl/SFC
2) Adapted ACR 50/70/90/100 response at week 4, 8, 12, 16, 20, and 24 since administration of 5-ALA-HCl/SFC
3) Corticosteroid dose reduction at week 4, 8, 12, 16, 20, and 24 since administration of 5-ALA-HCl/SFC
4) Change in corticosteroid dose from baseline at week 4, 8, 12, 16, 20, and 24 since administration of 5-ALA-HCl/SFC
5) Achievement of 20% dose reduction of corticosteroids at week 4, 8, 12, 16,20, and 24 since administration of 5-ALA-HCl/SFC
6) Change from baseline in systemic feature score at week 4, 8, 12, 16, 20, and 24 since administration of 5-ALA-HCl/SFC
7) Change from baseline in serum ferritin levels at week 8, 16, and 24 since administration of 5-ALA-HCl/SFC
8) Change from baseline in EQ-5D-5L at week 4, 8, 12, 16, 20, and 24 since administration of 5-ALA-HCl/SFC
Safety endpoints
1) Adverse events (incidence rate of adverse events, incidence rate of serious adverse events, incidence rate of adverse reactions)
2) Laboratory tests (hematology, blood biochemistry, urinalysis)
3) All medically important indicators (physical examination, vital signs, imaging studies, 12-lead ECG, etc.)

+81-95-819-7256

July. 19, 2022

none