A phase II investigator-initiated randomized, double blind, parallel-group clinical 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: jRCT2071220040

Registered date:18/08/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Adult Onset Still's Disease
• Date of first enrollment: 06/12/2022
• 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
Control group: Placebo orally twice daily

Outcome(s)

• Primary Outcome: Adapted ACR 30 response at week 4

Secondary Outcome

Efficacy endpoints
1) Adapted ACR 30 response at week 2, 6, and 8
2) Adapted ACR 50/70/90/100 response at week 2, 4, 6, and 8
3) Corticosteroid dose reduction at week 8
4) Change in corticosteroid dose from baseline at week 8
5) Achievement of 20% dose reduction of corticosteroids at week 8
6) Change from baseline in systemic feature score at week 4 and 8
7) Change from baseline in serum ferritin levels at week 4 and 8
8) Change from baseline in EQ-5D-5L at week 4 and 8
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 are 16 years of age or older at the time consent is obtained, any gender is acceptable
2) Patients who confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi et al. 1992) with an onset of disease 16 years of age or older 3) Patients with a history of refractory to treatment with corticosteroids at a prednisolone equivalent of 0.4 mg/kg/day or more for at least 2 weeks
4) Patients with all of the following a-c disease activity during the screening period despite taking prednisolone equivalent of 10 mg/day or more at a fixed dose for at least one week prior to obtaining consent
a. Patients with fever> 38 degrees Celsius for even one day due to AOSD
b. Patients with an active joint count (tender (68 joints) or swollen (66 joints)) of 2 or more
c. Patients with ESR (Westergren method)> 20 mm/h or CRP> 1.0 mg/dL
5) Patients whose free will informed consent can be obtained in writing and who are able to 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
6) Females of childbearing potential or Males who are sexually active with females of childbearing potential who agree to use an effective contraceptive method (e.g., condom) for the duration of the study and until the day after the last dose of study drug

Exclude criteria

1) Females who are lactating, pregnant, or intend to become pregnant during the study period
2) Patients with serious infections (including active tuberculosis)
3) Patients who received live vaccinations within 12 weeks prior to obtaining consent
4) Patients with HBV antibody, HCV antibody, or HIV antibody positive by screening test
Patients with a positive HBsAb or HBcAb test are eligible if HBV-DNA is negative
Patients with positive HCV antibodies are eligible only if the polymerase chain reaction (PCR) test is negative for HCV-RNA
5) Patients with complications or history of porphyria/ photosensitivity
6) Patients with hemochromatosis
7) Patients with known allergy or hypersensitivity or intolerance to aminolevulinic acid, sodium ferrous citrate, porphyrin, or their additives
8) Patients with a history of macrophage activation syndrome (MAS) or disseminated intravascular coagulation syndrome within 12 weeks prior to obtaining consent
9) Patients on dialysis
10) Patients with severe liver dysfunction (either AST or ALT exceeding 5 times the upper limit of the institutional reference value at the time of screening test)
11) Patients who used ALA-containing or iron-based drugs or supplements within 1 week prior to enrollment
12) Patients who used canakinumab, infliximab, or infliximab biosimilar within 12 weeks prior to enrollment
13) Patients who used golimumab, adalimumab, adalimumab biosimilar, certolizumab pegol, or abatacept within 8 weeks prior to enrollment
14) Patients who used tocilizumab or sarilumab within 4 weeks prior to enrollment
15) Patients who used etanercept or etanercept biosimilar within 2 weeks prior to enrollment
16) Patients who used any other biologic within either 12 weeks prior to enrollment or within 5 times the mean elimination half-life
17) Patients who used targeted synthetic DMARDs such as tofacitinib, baricitinib, peficitinib, upadacitinib, or filgotinib within 2 weeks prior to enrollment
18) Patients who used immunosuppressive drugs (oral) such as cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, or mizoribine within 2 weeks prior to enrollment
19) Patients who used intravenous cyclophosphamide or other immunosuppressive drugs (intravenous) within 4 weeks prior to enrollment
20) Patients who have changed doses of methotrexate or other disease-modifying anti-rheumatic drugs within 4 weeks prior to enrollment
21) Patients who are receiving another investigational drug or have not received their last dose for 30 days or 5 times the half-life of the investigational drug, whichever is longe
22) Patients with a serious complication for which the investigator or subinvestigator determines that they are not suitable for the clinical study
23) 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