A Phase 1/2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of IMPT-514 in Participants with Active, Refractory Lupus Nephritis and Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Phase II: Cohort 2 (SLE): Proportion of participants achieving definition of remission in SLE (DORIS) at Month 6.
研究概览
简要总结
This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with active, refractory lupus nephritis and systemic lupus erythematosus.
IMPT-514 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Individual participants will remain in the active post-treatment period for approximately 1 year.
Participants will continue in long-term follow-up for 15 years from treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent
- •Age 18 years of age or older
- •Weight > 45 kg at enrollment
- •Adequate blood pressure control
- •On stable background therapy for autoimmune disease (LN, SLE) with stable dose of autoimmune disease medications for at least 4 weeks prior to screening
- •Diagnosis of SLE by 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria or 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, including positive ANA or positive anti-dsDNA
- •Positive anti-nuclear antibody (ANA), anti-dsDNA (double stranded DNA) or anti-Smith antibody at screening
- •SLE participants: SLEDAI-2K ≥ 6 points, with at least 4 points on clinical, non-laboratory items
- •SLE participants: British Isles Lupus Assessment Group (BILAG) 2004 level B in 2 or more organ systems, or BILAG level A in 1 or more organ system
- •Physician Global assessment ≥ 1 on 0 to 3 visual analogue scale (VAS)
- •LN participants: Active, biopsy-proven, proliferative LN Class III or IV by 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
- •Other protocol-defined criteria apply.
- •Exclusion criteria:
- •Any clinically significant underlying illness, other than SLE and LN, which would pose a safety risk or concern, as determined by the Investigator
- •Any other systemic autoimmune condition
- •Rapidly progressive glomerulonephritis
- •Active central nervous system (CNS) lupus
- •History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation
- •History of prior B cell directed cell therapy, including CAR T treatment, autologous or allogeneic, as well as prior bispecific or T cell engager therapy
- •Drug-induced SLE
- •Other protocol-defined criteria apply.
排除标准
- 未提供
研究组 & 干预措施
Phase 1 Lupus Nephritis
Administration of IMPT-514
干预措施: IMPT-514 (Biological)
Phase 2 Lupus Nephritis
Administration of IMPT-514
干预措施: IMPT-514 (Biological)
Phase 2 SLE without Lupus Nephritis
Administration of IMPT-514
干预措施: IMPT-514 (Biological)
结局指标
主要结局
Phase II: Cohort 2 (SLE): Proportion of participants achieving definition of remission in SLE (DORIS) at Month 6.
时间窗: Baseline to Month 6
Phase I: Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other treatment-emergent adverse events (TEAEs).
时间窗: Baseline to Month 6
Phase I: Incidence of TEAEs, percent reduction in peripheral B cells, and the proportion of enrolled participants who receive the target dose.
时间窗: Baseline to Month 6
Phase II: Cohort 1 (LN): Proportion of participants with Complete Renal Response (CRR) as defined by EULAR/ERA-EDTA at Month 6.
时间窗: Baseline to Month 6
次要结局
未报告次要终点