A Phase 2, Open-Label, Single-Arm Trial of FT819 in Participants With Refractory Moderate-to-Severe Systemic Lupus Erythematosus With Lupus Nephritis (RECLAIM-LN)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 12
- 主要终点
- Complete Renal Response (CRR) at Week 26
研究概览
简要总结
The primary objective of this trial is to evaluate the efficacy and safety of FT819, comprised of allogeneic T cells that express a CD19-targeted CAR, following bendamustine administration in participants with refractory moderate-to-severe lupus nephritis, as assessed by the proportion of participants who achieve complete renal response (CRR) at Week 26.
详细描述
This is a multicenter, phase 2 single-arm trial designed to evaluate the efficacy and safety of FT819 in participants with moderate-to-severe systemic lupus erythematosus (SLE) with Class III/IV lupus nephritis (LN) (with or without concomitant Class V involvement) refractory to at least 2 immunosuppressive therapies prior to trial intervention.
Participants will undergo a screening period of up to 28 days. Following screening, trial intervention will consist of bendamustine administration followed by a single dose of FT819. Efficacy, safety, and exploratory assessments will be conducted at predefined timepoints through Month 24 of post-treatment follow-up (PTFU). Following completion of these scheduled assessments, participants will continue in long-term follow-up (LTFU) for up to 15 years after FT819 administration to monitor ongoing safety and survival.
Efficacy and disease activity will be assessed using standard LN measures, including complete renal response (CRR) and PRR (partial renal response), as well as clinician-reported outcomes, such as the SLEDAI-2K, BILAG, and PGA, performed at specified timepoints.
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
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥12 to ≤70 years
- •Diagnosis of SLE per EULAR/ACR 2019 classification criteria
- •Biopsy-proven proliferative Class III or IV LN, with or without concomitant Class V involvement, based on the 2003/2018 ISN/RPS classification
- •Positivity for at least one of the following autoantibodies at screening:
- •Antinuclear antibody (ANA)
- •Anti-double-stranded DNA (anti-dsDNA) or
- •Anti-Smith antibody
- •Active disease, defined as:
- •a. Evidence of SLE activity, defined as either: i. SLEDAI-2K ≥6 or ii. At least 1 BILAG A or 2 BILAG B scores for SLE-related organ involvement; and b. Evidence of renal involvement, defined as UPCr ≥1 g/g; and c. Moderate-to-severe renal disease with investigator's impression that improvement is possible
- •Refractory to ≥2 systemic immunosuppressive therapies for the treatment of LN
排除标准
- •Evidence of inadequate organ function during the screening period
- •Active central nervous system (CNS) symptoms attributable to autoimmune disease within 12 months prior to trial intervention
- •History of or current renal diseases (other than LN) that, in the opinion of the investigator, could interfere with assessment of LN or confound evaluation of disease activity
- •Receipt of dialysis (hemodialysis or peritoneal dialysis) within 12 weeks of trial intervention
- •Irreversible organ damage related to underlying disease (e.g., ESRD) where, in the opinion of the investigator, CD19 CAR T-cell therapy would be unlikely to benefit the participant
- •History of malignancy in the prior 5 years
- •Known allergy to the following FT819 components: albumin (human) or DMSO
- •History of intolerance or contraindication to bendamustine
- •Body weight <30 kg
- •Any medical condition, clinical laboratory abnormality, or nonmedical/social issue that, per investigator or medical monitor judgement, precludes safe participation in and completion of the trial or that could affect compliance with protocol conduct or interpretation of results
研究组 & 干预措施
FT819
FT819, allogeneic T cells derived from a clonal, TCR knockout iPSC line that express CD19-targeted CAR regulated by the TRAC locus, given as a single IV infusion
干预措施: FT819 (Biological)
结局指标
主要结局
Complete Renal Response (CRR) at Week 26
时间窗: Week 26
Proportion of participants achieving CRR at Week 26, with CRR defined as the achievement of all of the following criteria: * UPCR \<0.5 g/g * Estimated glomerular filtration rate (eGFR) ≥85% of baseline or ≥60 mL/min/1.73 m2 * No use of rescue therapy
次要结局
- Lupus Low Disease Activity State (LLDAS)(Up to approximately 2 years)
- CRR at Week 52(Week 52)
- CRR at Week 104(Week 104)
- Overall Renal Response(Up to approximately 2 years)
- Proportion of participants who achieve PRR at Week 26, Week 52, and Week 104(Up to approximately 2 years)
- Definition of Remission in SLE (DORIS)(Up to approximately 2 years)
- Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Up to approximately 2 years)
- Proportion of participants who achieve SLE Responder Index-4 (SRI-4)(Up to approximately 2 years)