A Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the CD19-Targeting Circular RNA Product RXIM002 in Patients With Relapsed or Refractory B Cell-Mediated Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Incidence and severity of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This Phase 1, open-label study evaluates the safety, tolerability, and preliminary efficacy of RXIM002, a CD19-targeting circular RNA-mediated in-vivo CAR T-cell therapy, in adults with severe, relapsed, or refractory B cell-mediated autoimmune diseases.
详细描述
This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of RXIM002 in adults with severe, relapsed, or refractory B cell-mediated autoimmune diseases. Eligible participants will receive intravenous administration of RXIM002 and will be monitored for adverse events, laboratory parameters, and other safety outcomes. The study will also explore biological activity and potential clinical responses across the enrolled autoimmune conditions. Participants will be followed for a defined period after treatment to assess longer-term safety and durability of any observed effects. The study will include the following sequential phases: screening, treatment, and follow-up.
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
- 18 Years 至 65 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 65 years, either sex.
- •Adequate organ function meeting screening criteria.
- •Positive test for cluster of differentiation antigen 19 (CD19).
- •Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN):
- •Have been diagnosed with SLE or LN before screening.
- •Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), antinuclear antibody (ANA), or anti-Sm antibodies at screening.
- •Active disease at screening.
- •Fulfill relapsed/refractory SLE or LN conditions
- •Lupus Nephritis (LN) :
- •Kidney biopsy result indicating LN
- •Evidence of LN disease activity
- •Systemic Sclerosis (SSc):
- •Have been diagnosed with SSc before screening.
- •Antinuclear Antibody (ANA) positive at screening or prior to screening. AND, evidence of SSc disease activity.
- •Fulfill relapsed/refractory SSc conditions.
- •Immune Thrombocytopenia (ITP):
- •Have been diagnosed with refractory ITP before screening.
- •Platelet count <50×10⁹/L at screening.
- •Idiopathic Inflammatory Myopathy (IIM):
- •Have been diagnosed with IIM before screening.
- •Presence of at least 1 myositis specific (MSA), associated antibody (MAA), or ANA at screening or prior to screening.
- •Evidence of IIM disease activity.
- •Fulfill relapsed/refractory IIM conditions.
- •Membranous Nephropathy (MN):
- •Have been diagnosed with MN before screening.
- •Active MN patients meeting screening criteria.
- •Fulfill relapsed/refractory MN conditions.
- •Autoimmune Hemolytic Anemia (AIHA):
- •Have been diagnosed with AIHA before screening.
- •Active AIHA patients meeting screening criteria.
- •Fulfill relapsed/refractory AIHA conditions.
排除标准
- •Active infections such as hepatitis and tuberculosis.
- •Other autoimmune diseases.
- •Serious underlying diseases such as active malignancies, uncontrolled diabetes.
- •Female subjects who were pregnant, breastfeeding.
- •Any uncontrolled psychiatric disorders (e.g., schizophrenia, bipolar disorder, eating disorders, major depression or anxiety disorder), as declared by the participant or reported in the medical records.
研究组 & 干预措施
RXIM002
Each study participant will be given 2 doses of RXIM002 at each dose level.
干预措施: RXIM002 product (Biological)
结局指标
主要结局
Incidence and severity of Dose-Limiting Toxicities (DLTs)
时间窗: 28 days after RXIM002 first infusion (Day 1)
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: 52 weeks after RXIM002 first infusion (Day 1)
CAR positive cell Cmax
时间窗: 24 weeks after RXIM002 first infusion (Day 1)
CAR positive T cells in peripheral blood after RXIM002 infusion, maximum concentration (Cmax).
CAR positive cell Tmax
时间窗: 24 weeks after RXIM002 first infusion (Day 1)
CAR positive T cells levels in peripheral blood after RXIM002 infusion, time to Cmax (Tmax).
CAR positive cell AUC
时间窗: 24 weeks after RXIM002 first infusion (Day 1)
CAR positive T cells levels in peripheral blood after RXIM002 infusion, area under the concentration-time curve (AUC) .
次要结局
- CircleRNA Cmax(24 weeks after RXIM002 first infusion (Day 1))
- LNP (Lipid Nanoparticle) Cmax(24 weeks after RXIM002 first infusion (Day 1))
- CircleRNA AUC(24 weeks after RXIM002 first infusion (Day 1))
- LNP (Lipid Nanoparticle) Tmax(24 weeks after RXIM002 first infusion (Day 1))
- LNP (Lipid Nanoparticle) AUC(24 weeks after RXIM002 first infusion (Day 1))
- CircleRNA Tmax(24 weeks after RXIM002 first infusion (Day 1))
- Lupus Nephritis (LN) disease activity: Proportion of subjects achieving Primary Efficacy Renal Response(PERR)(52 weeks after RXIM002 first infusion (Day 1))
- Systemic Lupus Erythematosus (SLE) disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(52 weeks after RXIM002 first infusion (Day 1))
- Systemic Sclerosis (SSc) disease activity :Modified rodnan skin score(mRSS)(52 weeks after RXIM002 first infusion (Day 1))
- Idiopathic Inflammatory Myopathy (IIM) disease activity ：Manual muscle test-8(52 weeks after RXIM002 first infusion (Day 1))
- Autoimmune Hemolytic Anemia (AIHA) disease activity: Overall Hb therapeutic response(8 weeks after RXIM002 first infusion (Day 1))
- Immune Thrombocytopenia (ITP) disease activity: Overall response of platelet increment.(8 weeks after RXIM002 first infusion (Day 1))
- Membranous Nephropathy (MN) disease activity: Clinical remission rate(52 weeks after RXIM002 first infusion (Day 1))