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

JRCT ID: jRCT2071220086

Registered date:07/01/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Adult Onset Still's Disease
• Date of first enrollment: 01/02/2023
• Target sample size: 30
• Study type: Interventional

Intervention(s)

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

Outcome(s)

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

Secondary Outcome

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.)

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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.

Exclude criteria

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.

Related Information

• Primary Sponsor: Kawakami Atsushi
• Source(s) of Monetary Support: Japan Afency for Medical Research and Development,KIYAN PHARMA