Efficacy and Safety of IL-1 Inhibitors in the Treatment of Mild to Moderate Systemic Lupus Erythematosus With Inadequate Response to Conventional Therapy: A Single-Centre, Single-Arm, Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- the percentage of patients achieving an BICLA response at the end of 12 weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Firsekibart group
Firsekibart combined with standard therapy: subcutaneous injection of 200mg Firsekibart at weeks 0, 4 and 8. Firsekibart monotherapy discontinued at weeks 12-24, with all other standard treatments unchanged. Observe for recurrence; if recurrence occurs, patients will be removed from the group and receive additional therapy.
干预措施: Firsekibart (Drug)
结局指标
主要结局
the percentage of patients achieving an BICLA response at the end of 12 weeks
时间窗: From enrollment to the end of treatment at 12 weeks
The BICLA response was defined as a reduction of all severe (BILAG-2004 A) or moderately severe (BILAG-2004 B) disease activity at baseline to lower levels (BILAG-2004 B, C, or D and C or D, respectively) and no worsening in other organ systems (with worsening defined as ≥1 new BILAG-2004 A item or ≥2 new BILAG-2004 B items); no worsening in disease activity, as determined by the SLEDAI-2K score (no increase from baseline) and by the PGA score (no increase of ≥0.3 points from baseline)
次要结局
- the percentage of patients achieving an BICLA response at the end of 24 weeks(From enrollment to the end of treatment at 24 weeks)
- the percentage of patients achieving SRI-4 response at the end of 12 weeks.(From enrollment to the end of treatment at 12 weeks)
- the percentage of patients achieving SRI-4 response at the end of 24 weeks.(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline in SLEDAI at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline in SLEDAI at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Changes from baseline in PGA at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline in PGA at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Changes from baseline of the SJC and TJC at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline of the SJC and TJC at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Changes from baseline of the levels of Erythrocyte Sedimentation Rate (ESR) at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline of the levels of Erythrocyte Sedimentation Rate (ESR) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Changes from baseline of the CLASI score at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline of the CLASI score at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Changes from baseline of the levels of C-Reaction Protein (CRP) at 24 weeks(From enrollment to the end of treatment at 24 weeks)
- Changes from baseline of the levels of C-Reaction Protein (CRP) at 12 weeks(From enrollment to the end of treatment at 12 weeks)