Adult-Onset Still's Disease
Conditions
Interventions
Firsekibart:Firsekibart will be administered according to the protocol.
Anakinra:Anakinra will be administered according to the protocol.
Sponsors
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Age: This study will include subjects aged 18 to 75 years (inclusive), regardless of gender. 2.Subjects must be willing to participate in the study and voluntarily sign an informed consent form. 3.Diagnosis of AOSD will be based on the Yamaguchi criteria: Major criteria: (1) Fever >=39°C lasting for >=1 week; (2) Arthralgia lasting for >=2 weeks; (3) Typical rash; (4) White blood cell count >=10×10^9/L with neutrophils >=80%. Minor criteria: (1) Sore throat or pharyngitis; (2) Lymphadenopathy and/or splenomegaly; (3) Abnormal liver function; (4) Negative rheumatoid factor and antinuclear antibody. Exclusion criteria: (1) Infectious diseases (especially sepsis and EBV infection); (2) Malignancies (especially lymphoma); (3) Other rheumatic diseases (particularly systemic vasculitis). After excluding the above exclusion criteria, a diagnosis of AOSD requires meeting >=5 of the above criteria (including at least 2 major criteria). 4.Activedisease is defined as meeting 2 Yamaguchi criteria along with the presence of fever or CRP >10 mg/L. 5.If currently receiving glucocorticoid therapy, the dose must have been stable for at least 1 week prior to randomization. The maximum allowed dose is 1 mg/kg/day. 6.Subjects (including their partners) must have no pregnancy plans from the screening period until 28 days after the last dose and must voluntarily use contraception.
Exclusion criteria
Exclusion criteria: Subject Exclusion Criteria: 1. Pre-randomization Medication: (1) Received any of the following treatments within 4 weeks prior to screening or within 5 known drug half-lives (whichever is shorter): BTK inhibitors, JAK inhibitors; Intravenous immunoglobulin; Plasmapheresis; Traditional Chinese medicine therapy (2) Received Anakinra treatment within 1 day prior to randomization; (3) Received Etoposide (VP-16) treatment within 12 weeks prior to the baseline visit; (4) Increased dosage or added new types of non-biologic agents for treating rheumatic/autoimmune diseases (e.g., immunosuppressants, immunomodulators, antimalarials) within 3 days prior to the baseline visit, unless the investigator determines the treatment is expected to be ineffective and was discontinued prior to baseline. Specific medications include: i Immunosuppressants/Immunomodulators: Methotrexate, Azathioprine, Leflunomide, Mycophenolate (including Mycophenolate Mofetil, Mycophenolate Mofetil Hydrochloride, Mycophenolate Sodium), Mizoribine, Calcineurin inhibitors (e.g., Tacrolimus, Cyclosporine), Sirolimus, Oral Cyclophosphamide, 6-Mercaptopurine, Thalidomide, Total Glucosides of Peony (Paeonia lactiflora Pall.) ii Antimalarials:e.g., Hydroxychloroquine, Chloroquine, Quinacrine. 2. Allergy History: History of allergy to any component of the investigational drug. 3. HLH at Baseline or Suspected HLH: Diagnosis of HLH within 2 months prior to randomization. Diagnosis according to the HLH-2004 criteria is defined as meeting either of the following two conditions: (1) Molecular diagnosis consistent with HLH; (2) Meeting at least 5 out of the following 8 criteria: 1) Fever: Temperature >38.5°C, lasting >7 days; 2) Splenomegaly; 3) Cytopenias (affecting =2 lineages in peripheral blood): Hemoglobin <100 g/L, Neutrophils <1.0 × 10?/L, and not due to reduced bone marrow function; 4) Hypertriglyceridemia and/or hypofibrinogenemia: Triglycerides =3 mmol/L or =3 SD above age-specific norms, Fibrinogen =1.5 g/L or =3 SD below age-specific norms; 5) Hemophagocytosis identified in bone marrow, spleen, or lymph nodes; 6) Elevated serum ferritin: Ferritin =500 µg/L; 7) Reduced or absent NK cell activity; 8) Elevated soluble IL-2 receptor (sCD25) =2400 U/mL. 4. Hematological Diseases:History or current diagnosis of hematological diseases (including but not limited to myelofibrosis, aplastic anemia, leukemia, lymphoma, etc.). 5. Cardiovascular Diseases:History of acute myocardial infarction, unstable angina, or severe arrhythmias (multifocal frequent ventricular premature beats, ventricular tachycardia, ventricular fibrillation, etc.) within the past 6 months; NYHA Class III-IV heart failure. 6. Pulmonary Diseases:Including but not limited to asthma, COPD, interstitial lung disease, pulmonary alveolar proteinosis, pulmonary granulomatosis, etc., AND with pulmonary function test abnormalities: FVC <80% predicted, or FEV1/FVC <70%; OR investigators' comprehensive assessment determines the subject has underlying lung disease significantly affecting pulmonary function, making participation unsuitable. 7. Malignancy History:History of malignancy within the past 5 years (regardless of treatment), except for successfully treated basal cell or squamous cell skin carcinoma. 8. Other Diseases:Presence of clinically significant, clinically unstable, or inadequately controlled acute or chronic diseases (e.g., acute pneumonia, pulmonary hypertension, diabetic ketoacidosis, acute pancreatitis, etc.), o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects achieving clinical inactive disease (CID) at Week 24, where CID is defined as the absence of Still's disease-related symptoms with normal ESR or CRP levels.; | — |
Countries
China
Contacts
Public ContactChengde Yang
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed