A Phase IIa, Open-Label, Single-Arm Study With an Initial Safety Run-In and Dose Expansion of ICG318 (BCMA-CD19-IL-15/IL15sushi cCAR T) in Participants With Refractory Systemic Lupus Erythematosus, With or Without Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Number of Adverse Events after ICG318 infusion
研究概览
简要总结
This Phase IIa, open-label, single-arm study includes an initial Safety Run-In followed by dose expansion to evaluate the safety, tolerability, cellular kinetics, pharmacodynamics, and preliminary clinical activity of a single infusion of ICG318 in participants with refractory SLE, with or without LN. Participants will receive protocol-specified lymphodepletion followed by ICG318 at the recommended Phase 2 dose.
详细描述
Systemic Lupus Erythematosus (SLE) is a multisystem, chronic autoimmune disease that may impact multiple organs including the joints, skin, kidney, heart, brain and lungs, with severity ranging from mild to life-threatening. Lupus Nephritis (LN) is the most prevalent and severe form of SLE with high morbidity and mortality and persistent relapses despite current therapies.
SLE, with or without LN is driven largely by pathogenic autoantibodies produced by CD19 expressing B cells and BCMA expressing plasma cells, including long-lived plasma cells.
ICG318, the investigational agent in this clinical trial is an armored, compound chimeric antigen receptor (CAR) composed of two independently functioning CARs that simultaneously target the B-cell CD19 surface antigen and the plasma cell/ long lived plasma cell BCMA surface antigen.
This study is being conducted to evaluate the safety and efficacy of ICG318 in SLE patients with or without LN, who have not shown adequate clinical response to prior therapies.
A single dose of ICG318 following a lymphodepletion regimen will be evaluated.
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
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16-70 years at the time of signing the informed consent
- •Have a diagnosis of SLE by EULAR/ACR 2019 criteria for ≥6 months.
- •Have at least one of an antinuclear antibody, anti-double-stranded deoxyribonucleic acid (dsDNA), or elevated anti-Smith (Sm) antibody
- •Inadequate response to 2 prior standard of care therapies, used for at least three months
- •SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥7 at Screening
- •For LN cohort participants. Kidney biopsy result within 6 months prior to Screening indicating Class III or IV (alone or in combination with Class V).
排除标准
- •Any acute, severe lupus related flare that needs immediate treatment
- •History of antiphospholipid syndrome with thromboembolic event within 12 months
- •History or current diagnosis of any disease, condition or treatment that may confound clinical assessments in the study.
- •Has drug-induced SLE.
- •History of prior CAR-T therapy.
- •History of bone marrow/hematopoietic stem cell or solid organ transplant or planned receipt during the study period.
- •Recent serious or ongoing infection, or risk for serious infection, or acute or chronic infection
- •Receipt of a live/live-attenuated vaccine other than BCG within 8 weeks
- •History within the past year or current clinically significant central nervous system disease, including but not limited to cerebrovascular accident, seizures, severe brain injury, dementia, Parkinson's disease, cerebellar disease, or multiple sclerosis
- •Impaired cardiac function or clinically significant cardiac disease
- •End stage renal disease or severe liver disease
- •Breastfeeding/lactating or pregnant women or women who intend to become pregnant at any time during the study.
研究组 & 干预措施
Single arm
Biologic drug infusion
干预措施: ICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR T following lymphodepletion (Biological)
结局指标
主要结局
Number of Adverse Events after ICG318 infusion
时间窗: Starting day 0 and up to 1 year after ICG318 infusion.
Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESI), and Dose Limiting Toxicities (DLTs).
DORIS remission rate
时间窗: Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.
DORIS remission defined as no circulating autoantibodies (e.g. dsDNA, Smith etc.) detected, no SLE medications, and SLEDAI-2K score of 0-1 (down from severe 7-10).
次要结局
- Tmax(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Determine the recommended phase 2 dose (RP2D) regimen.(Starting day 0 and assessed 1 year after ICG318 infusion.)
- Cmax(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- T1/2(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Complement levels(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- AUC(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Rate of B cell elimination and naïve B-Cell recovery(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Recovery of immunoglobulins(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- SLE Autoantibody levels(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Number of patients achieving DORIS remission, LLDAS, Complete or Partial Renal Response (in LN patients)(Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.)
- Renal histology(The first biopsy will be obtained prior to ICG318 infusion. Next biopsy will be assessed up to 6 months to 1 year after ICG318 infusion.)
- Serum creatinine levels(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- eGFR value(Assessed as per schedule of events up to 1 year after ICG318 infusion.)
- Urine Protein-Creatinine Ratio (uPCR) levels.(Assessed as per schedule of events up to 1 year after ICG318 infusion.)