Study summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder in which pro-inflammatory factors of the IL-1 family play a pivotal role in its pathogenesis. In SLE patients, an innate immune hyperreactivity coupled with excessive inflammasome activation leads to substantial IL-1β production, triggering inflammatory phenotypes such as fever and serositis. For SLE patients unresponsive to conventional therapies, particularly those exhibiting high fever and serositis indicative of innate immune overactivation, effective targeted treatments remain scarce. Firsekibart, as a first anti-IL-1β biologic, holds promise in delivering novel therapeutic benefits for SLE patients with high-inflammatory phenotypes who prove refractory to standard therapies.
Eligibility
Inclusion Criteria:
* Aged 18 to 65 years, male or female; female participants must not be pregnant or breastfeeding and must agree to use effective contraception during the trial period.
* Meets the 2012 SLICC classification criteria for SLE or the 2019 ACR/EULAR classification criteria for SLE;
* Mild to moderate disease activity, 1 point ≤ SLEDAI ≤ 12 points (cSLEDAI ≠ 0);
* The presence of at least one of the following recent clinical manifestations: fever (excluding fever caused by infection, tumor, endocrine or metabolic disorders, central nervous system diseases, medications, or physical factors), serositis (such as pericarditis or pleurisy), arthritis, rash, or alopecia;
* ESR or CRP exceeds the upper limit of normal, i.e. ESR \> 20 mm/h or CRP \> 10 mg/L;
* Patients had received standard therapy prior to study drug administration: ≤1 immunosuppressive agent for at least 12 weeks (methotrexate ≤15 mg/week, azathioprine ≤100 mg/day, mycophenolate mofetil ≤1.5 g/day, tacrolimus ≤2 mg/day, cyclosporine ≤150 mg/day, sirolimus ≤1.5 mg/day); Hydroxychloroquine (HCQ) may be used; Patients previously treated with biologics (e.g., Belimumab, Telitacicept, Anifrolumab) with inadequate response may also be considered for inclusion, provided they undergo a washout period of three half-lives during screening.
* The patient voluntarily participated in this trial, demonstrated good compliance, and possessed the capacity to understand and sign the informed consent form prior to the study.
Exclusion Criteria:
* SLE with major organ dysfunction, including impaired consciousness, cognitive decline, renal insufficiency, cardiac insufficiency (NYHA class 3 or 4), pulmonary hypertension, and pulmonary interstitial disease.
* Active SLE organ involvement, including but not limited to active lupus encephalopathy, active lupus nephritis (proteinuria ≥1g/24h), cardiac involvement, gastrointestinal involvement, diffuse alveolar haemorrhage, thrombocytopenic purpura, hemophagocytic syndrome, and retinopathy.
* SLE coexisting with other autoimmune diseases potentially affecting efficacy assessment, including but not limited to rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.
* Abnormal liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times the upper limit of normal; total bilirubin (TBIL) \> 1 times the upper limit of normal.
* Any active malignancy or history of malignancy within the preceding five years.
* Concurrent conditions requiring glucocorticoid therapy, such as asthma or Crohn's disease.
* Acute or chronic infections requiring anti-infective treatment, including but not limited to tuberculosis, HBV or HCV infection, HIV infection, or CMV infection.
* Major surgical procedures within the preceding three months.
* Hypersensitivity or intolerance to Firsekibart; individuals with known hypersensitivity to Chinese hamster ovary (CHO) cell-derived products should also be excluded (Firsekibart is a recombinant monoclonal antibody with potential residual CHO expression risk).
* Pregnancy, planned pregnancy, or lactation.
* Use of biological agents within 3 months prior to enrolment, including but not limited to CD20 monoclonal antibodies (e.g., rituximab), B-lymphocyte stimulatory factor inhibitors (e.g., belimumab, telitacicept), or TNF-α inhibitors (e.g., adalimumab, infliximab).
* Receipt within 3 months prior to enrolment of high-dose glucocorticoids (prednisolone or equivalent ≥60mg qd), plasma exchange, IVIG, or oral/intravenous cyclophosphamide.
* Individuals who have received live attenuated vaccines (e.g., varicella, herpes zoster, intranasal influenza vaccines) within 3 months prior to enrolment, or who plan to receive live vaccines during the study period.
* Any condition deemed by the investigator to potentially prevent the subject from completing the study or pose a significant risk to the subject.