狼疮肾炎治疗药物临床试验设计的一般技术考虑

General Technical Considerations for the Design of Clinical Trials of Drugs for the Treatment of Lupus Nephritis

目的 探讨狼疮肾炎治疗药物临床试验设计的一般技术考虑。方法 通过调研国内外相关技术标准、梳理总结已上市新药研发经验,基于疾病特点、治疗需求并结合审评实践,从技术审评角度探讨狼疮肾炎药物临床试验总体设计、入选人群标准、疗效指标及安全性评价等,提出技术考虑要点。结果与结论研究设计推荐采用多中心、随机、双盲、平行对照设计,一般在标准治疗的基础上进行研究。入选人群在随机分组前6个月内进行肾活检更能够代表基线特征。疗效评价指标设计方面,单一指标不足以充分反映药物的有效性,通常采用复合指标进行评估,推荐使用完全肾脏缓解率作为主要疗效评价指标。完全肾脏缓解的标准应能代表肾功能有临床意义的显著改善。次要疗效指标的设计应基于狼疮肾炎的临床治疗目标多维度考虑,包括评估减少糖皮质激素和/或免疫抑制剂的用药剂量、长期肾脏结局(进展为终末期肾病)以及系统性红斑狼疮(systemic lupus erythematosus,SLE)表现和SLE总体活动性等。安全性方面应特别监测感染、心血管事件和恶性肿瘤的风险以及新药对肾功能的潜在影响。

OBJECTIVE To explore general technical considerations for the clinical trial design of drugs targeting lupus nephritis treatment.METHODS By conducting comprehensive research on relevant technical standards both domestically and internationally,synthesizing the experience gained from recent drug development endeavors,and integrating disease characteristics,treatment requirements,and evaluation practices,the holistic design of clinical trials for lupus nephritis drugs were explored from a technical evaluation perspective which including examining participant selection criteria,efficacy indicators,safety evaluations,and proposing key technical considerations.RESULTS and CONCLUSION The recommended research design is a multicenter,randomized,double-blind,parallel-controlled design typically conducted using standard treatment protocols.Including participants who have undergone renal biopsy within 6 months prior to randomization can enhance the representation of baseline characteristics.In terms of efficacy evaluation indicators,relying solely on a single indicator is insufficient to fully capture the effectiveness of the drug;therefore,composite indicators are commonly employed for comprehensive assessment purposes.The primary efficacy evaluation indicator should be the complete renal remission rate,with criteria that accurately reflect clinically significant improvement in kidney function.Secondary efficacy indicators should encompass multiple dimensions aligned with clinical treatment goals for lupus nephritis and include assessments of glucocorticoid and/or immunosuppressant dosage reductions,long-term renal outcomes(such as progression to end-stage kidney disease),as well as evaluations of SLE manifestations and overall activity levels.Safety aspects necessitate vigilant monitoring for risks such as infection,cardiovascular events,malignant tumors,and potential impacts on renal function posed by novel drugs.