Multi-center, Phase 2 Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T Cell Therapy (C-CAR168) for the Treatment of Lupus Nephritis Refractory to Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Complete Renal Response (CRR)
研究概览
简要总结
This Phase 2, multicenter, open-label study will evaluate the safety and efficacy of a single infusion of autologous anti-CD20/BCMA chimeric antigen receptor T cells (C-CAR168) following lymphodepleting chemotherapy in participants with refractory lupus nephritis who are not responding to standard therapy.
Approximately 50 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of C-CAR168. Participants will be followed for 104 weeks (approximately 2 years) to evaluate renal response, safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, and biomarkers. Long-term safety follow-up for gene therapy-related events will continue for up to 15 years following CAR T-cell infusion.
详细描述
This is a global, multicenter, single-arm, open-label Phase 2 study evaluating C-CAR168, an autologous dual-targeted anti-CD20/BCMA CAR T-cell therapy, in participants with biopsy-confirmed refractory lupus nephritis who are not responding to standard therapy.
Participants will undergo screening, leukapheresis, manufacture of autologous C-CAR168, lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide, followed by a single intravenous infusion of C-CAR168.
The study begins with a safety run-in involving the first five participants. Following review by the Safety Monitoring Committee (SMC), enrollment of the remaining participants may proceed if predefined safety criteria are met.
Participants will be followed for 104 weeks after infusion for evaluation of efficacy, safety, pharmacokinetics, pharmacodynamics, immunologic biomarkers, and patient-reported outcomes. Participants will subsequently be invited to enroll in a separate long-term follow-up study for continued safety monitoring consistent with FDA recommendations for gene-modified cellular 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
- 14 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide informed consent or assent where applicable.
- •Male or female aged 14-70 years, weighing at least 40 kg.
- •Diagnosis of systemic lupus erythematosus according to the 2019 EULAR/ACR classification criteria.
- •Biopsy-confirmed ISN/RPS Class III or IV lupus nephritis, with or without Class V, within 6 months before screening.
- •Proteinuria meeting protocol-defined thresholds.
- •Refractory to standard therapy.
- •Meets corticosteroid taper requirements.
- •Positive ANA and/or anti-dsDNA and/or anti-Smith antibody.
- •Meets all protocol eligibility requirements.
排除标准
- •Active uncontrolled infection
- •Active hepatitis B, hepatitis C, or HIV infection
- •Active tuberculosis
- •Pregnancy or breastfeeding
- •Prior gene therapy or CAR T-cell therapy
- •Active malignancy
- •Severe cardiovascular disease
- •Significant pulmonary disease
- •CNS disease precluding participation
- •Any condition that would interfere with study participation or safety
研究组 & 干预措施
C-CAR168
Participants will receive:
- Leukapheresis
- Fludarabine
- Cyclophosphamide
- Single intravenous infusion of C-CAR168
干预措施: C-CAR168 (Drug)
结局指标
主要结局
Complete Renal Response (CRR)
时间窗: Week 65 (Month 15)
Proportion of participants achieving Complete Renal Response according to protocol-defined criteria.
次要结局
- Incidence and severity of adverse events (AEs)(Through Week 104 (Month 24))
- incidence of serious adverse events (SAEs)(Through Week 104 (Month 24))
- Incidence and severity of cytokine release syndrome (CRS)(Through Week 104 (Month 24))
- Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS)(Through Week 104 (Month 24))
- Duration of Complete Renal Response (CRR)(Through Week 104 (Month 24))
- Partial Renal Response (PRR)(Through Week 104 (Month 24))
- Primary Efficacy Renal Response (PERR)(Through Week 104 (Month 24))
- Reduction in proteinuria(Through Week 104 (Month 24))
- Time to renal response(Through Week 104 (Month 24))
- Pharmacokinetics of C-CAR168 measuring quantitative polymerase chain reaction (qPCR)(Through Week 104 (Month 24))
- Pharmacokinetics of C-CAR168 utilizing flow cytometry(Through Week 104 (Month 24))
- Change in patient-reported outcomes (PROs)(Through Week 104 (Month 24))
- DORIS remission(Though Week 104 (Month 24))
- Progressive renal failure(Through Week 104 (Month 24))
- Corticosteroid reduction(Through Week 104 (Month 24))
- Lupus disease flare(Through Week 104 (Month 24))
- Immunologic response(Through Week 104 (Month 24))