Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus: a Randomised Prospective Study
试验速览
- 阶段
- 3 期
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Immunological responses of B cell subsets
研究概览
简要总结
The purpose of this study was to explore the clinical and immunological efficacy of belimumab plus low dose IL-2 in systemic lupus erythematosus.
详细描述
Given that belimumab and low dose interleukin-2 (IL-2) have been widespreadly applied in the treatment of systemic lupus erythematosus (SLE), this study designed a randomised, single center, prospective study to investigate the effects and safety of combined utilization of belimumab and low dose IL-2. SLE patients were allocated in each group randomly (n=10) and regularly administered belimumab (10mg/kg) with or without IL-2 (1 million IU). Then, we evaluated the improvement of clinical and laboratory indexes and monitored the changes of immune cell subsets and cytokines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female >18 years of age at screening visits
- •Patients meet the American-European Consensus Group 2002 classification criteria
- •The patient must be informed in writing of the consent to participate in the trial and the patient is expected to be able to comply with the requirements of the study follow-up plan and other protocols.
- •Dosing of antimalarials, prednisone or equivalent, cholinergic stimulants, and topical cyclosporine required to be stable for at least 4 weeks before screening and during study; maximum doses allowed:
- •Hydroxychloroquine, 400 mg/day;
- •Prednisone, 10 mg/day
排除标准
- •Any subject meeting any of the following criteria should be excluded:
- •Laboratory abnormality: • Hb≤9 g/dl • Neutrophil 10 mg/d) within 1 month.
- •Serious complications: including heart failure (≥ New York Heart Association (NYHA) class III), renal insufficiency (creatinine clearance ≤ 30 ml/min), liver dysfunction (serum Alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of normal, or total bilirubin greater than Normal upper limit)
- •Known allergies, hyperreactivity or intolerance of tofacitinib or its excipients.
- •Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus (EBV), tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.
- •Infection with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, it is recommended to consult a doctor who has expertise in treating HIV or hepatitis C virus infection.
- •Any known history of malignancy in the past 5 years (except for nonmelanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).
- •Uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past 3 years, may hinder the successful completion of the study.
- •Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.
研究组 & 干预措施
belimumab plus low dose IL-2
10mg/kg belimumab was intravenously injected to patients with systemic lupus erythematosus every month for 24 weeks.
Interleukine-2 was first added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh, then the same dose of IL-2 was injected once a week for 12 weeks subcutaneously.
干预措施: Belimumab (Drug)
belimumab plus low dose IL-2
10mg/kg belimumab was intravenously injected to patients with systemic lupus erythematosus every month for 24 weeks.
Interleukine-2 was first added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh, then the same dose of IL-2 was injected once a week for 12 weeks subcutaneously.
干预措施: Interleukin-2 (Drug)
belimumab
10mg/kg belimumab was administrated to patients with systemic lupus erythematosus for at least 24 weeks, intravenously injected every month.
干预措施: Belimumab (Drug)
low dose IL-2
The first stage: interleukine-2 was added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh; The second stage: 1 million IU IL-2 was injected once a week for 12 weeks subcutaneously.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Immunological responses of B cell subsets
时间窗: Week 24
A significant reduction of active B cell subsets including naive B cells and transitional B cells after different interventions. P values below 0.05 are considered statistically significant in this study.
次要结局
- Proportion of SLE Responder Index (SRI)4 response(Week 12 and 24)
- Prednisone dose(Week 12 and 24)
- Immunoglobulin change from baseline(Week 12 and 24)
- Autoantibody change from baseline(Week 12 and 24)
- Change of complement C3 and C4 Levels from baseline(Week 12 and 24)
- Safety and tolerability of the treatment(Up to Week 24)