An Open-label Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LUCAR-DKS1 in Subjects With Relapsed/Refractory Autoimmune Diseases (r/r AID)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 5
- 主要终点
- Tmax
研究概览
简要总结
This is a prospective, single-arm, open-label and dose-escalation Investigator Initialed study to evaluate LUCAR-DKS1 in adult subjects with relapsed/refractory autoimmune diseases.
详细描述
This is a prospective, single-arm, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy profiles of LUCAR-DKS1, a chimeric antigen receptor (CAR) -NK cell therapy in subjects with relapsed/refractory autoimmune diseases. Patients who meet the eligibility criteria will receive LUCAR-DKS1 infusion. The study will include the following sequential stages: screening, pre-treatment (lymphodepleting chemotherapy), treatment LUCAR-DKS1 infusion) and follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntary agreement to provide written informed consent.
- •Aged 18 to 70 years, either sex.
- •Clinical laboratory values meet screening criteria.
- •Positive test for CD19 and/ or BCMA
- •Meets at least 1 classification criteria≥6 months for SLE.
- •At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody should be positive.
- •Fulfill relapsed/refractory SLE conditions.
- •Meets the 2022 ACR/EULAR classification criteria for AAV.
- •Positive test for anti-MPO or p-ANCA or anti-PR3 or anti-MPO antibodies at screening.
- •Fulfill relapsed/refractory AAV conditions.
- •Meets the 2013 ACR/EULAR classification criteria for SSc.
- •At screening, mRSS is higher than
- •Fulfill relapsed/refractory SSc conditions.
- •Meets 2017 EULAR/ACR classification criteria for IIM.
- •Positive test for myositis-associated antibodies or myositis-specific antibodies at screening.
- •Fulfill relapsed/refractory IIM conditions. SjS：
- •Meets the 2016 ACR/EULAR diagnostic criteria for SjS.
- •Positive test for anti-SSA and/or anti-SSB antibodies at screening.
- •Fulfill relapsed/refractory SjS conditions.
排除标准
- •Active infections such as hepatitis and tuberculosis.
- •Other autoimmune diseases.
- •Serious underlying diseases such as tumor, uncontrolled diabetes.
- •Female subjects who were pregnant, breastfeeding.
- •Those with a history of major organ transplantation.
- •Have received autologous cell therapy of any target before.
研究组 & 干预措施
Chimeric antigen receptor NK cells (LUCAR-DKS1), single-dose for each subject.
Experimental: chimeric antigen receptor NK cells (LUCAR-DKS1). Dose level1：25 millions /kg Dose level2：50 millions /kg Dose level3：100 millions /kg Dose level4：200 millions /kg Dose level5：400 millions /kg Totally 5 dose groups, each subject will be given a single-dose LUCAR-DKS1 cells infusion at a certain level, subject will be administered at day 1.
干预措施: LUCAR-DKS1 NK cells (Biological)
结局指标
主要结局
Tmax
时间窗: About 2 years after LUCAR-DKS1 infusion (Day 1)
CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion, time to Cmax (Tmax).
Incidence, severity, and type of treatment-emergent adverse events (TEAEs) .
时间窗: About 2 years after LUCAR-DKS1infusion (Day 1)
≥Grade 1 clinical symptoms, laboratory test abnormalities, and clinical events that are possibly, likely, or definitely related to study treatment. Accessed by CTCAE5.0.
Incidence of dose-limiting toxicity (DLT)
时间窗: About 2 years after LUCAR-DKS1 infusion (Day 1)
DLTs are severe adverse events that refers to any untoward medical occurred in a subject participated in a clinical investigation, which have a causal relationship with the treatment and will limit the dose escalation.
Cmax
时间窗: About 2 years after LUCAR-DKS1 infusion (Day 1)
CAR positive NK cells in peripheral blood after LUCAR-DKS1 infusion, maximum concentration (Cmax).
AUC
时间窗: About 2 years after LUCAR-DKS1 infusion (Day 1)
CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion， area under the concentration-time curve (AUC) .
Recommended phase 2 dose regimen finding
时间窗: About 2 years after LUCAR-DKS1 infusion (Day 1)
Recommended phase 2 dose regimen established through dose exploratoration finding.
次要结局
- SLE disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(About 2 years after LUCAR-DKS1infusion (Day 1))
- SSc disease activity :Modified rodnan skin score(mRSS)(About 2 years after LUCAR-DKS1 infusion (Day 1))
- AAV disease activity： Birmingham vasculitis activity score (BVAS)(About 2 years after LUCAR-DKS1 infusion (Day 1))
- IIM disease activity ：Manual muscle test-8(About 2 years after LUCAR-DKS1 infusion (Day 1))
- SjS disease activity: Sjögren's Tool for Assessing(STAR)(About 2 years after LUCAR-DKS1 infusion (Day 1))