An Exploratory Clinical Study of Enhanced Autologous CAR-T Cell Injection (ECAR01) Targeting BCMA and CD19 in the Treatment of Refractory Autoimmune Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This is an open label, single-site, dose-escalation study in up to 18 participants with refractory autoimmune diseases. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART
详细描述
This study is a single-center, single-arm, non-blinded, 3+3 dose-escalation designed investigator initiated trial study, evaluating the safety, efficacy, and therapeutic assessment of ECAR01 injection in patients with refractory autoimmune diseases. The specific research protocol can be adjusted by the researchers based on the patient's condition. Patients with refractory autoimmune diseases who meet the inclusion and exclusion criteria are included. After peripheral blood collection and chemotherapy pretreatment, the subjects undergo CAR-T cell infusion. The three dose groups are the low-dose group (1×10^5/kg, number of CAR-T cells per kg of subject's weight, the same below), the medium-dose group (3×10^5/kg), and the high-dose group (6×10^5/kg). Clinicians can also adjust the drug dose based on actual conditions. Given the particularity of cell preparation doses, each dose group allows for a ±20% fluctuation in the actual drug dose.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •( 1) At the time of signing the informed consent form, be at least 18 years of age, both male and female.
- •(2) Bone marrow hematopoietic function satisfies: white blood cell count≥3×10^9/L; Centrocyte count ≥1×10^9/L (no colony-stimulating factor received within 2 weeks prior to screening); Hemoglobin ≥ 60g/L.
- •(3)ALT≤3×ULN; AST≤3×ULN； TBIL≤3×ULN。 (4) Renal function satisfaction: creatinine clearance CrCl≥30mL/min. (5) INR≤1.5×ULN , PT≤1.5×ULN. (6)RA:Documented diagnosis of RA which fulfills the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria ; 3 months after use of 1 or more csDMARDs and 1 or more bDMARDs prior to screening: 1) DAS28-ESR>3.2 or CDAI>10; or 2) the dose of the hormone (prednisone or equivalent) cannot be reduced to less than 7.5 mg/day; or 3) the number of swollen and/or tender joints ≥3; Treatment with stable 1 or more cs DMARD(s) and/or bDMARDs prior to enrollment as follows: methotrexate for at least 12 weeks and at a dose of 7.5-25mg/week for at least 4 weeks; Stable use of hydroxychloroquine dose ≤ 400 mg/day for at least 4 weeks; Stable oral sulfasalazine for at least 4 weeks 1~3 g/d; Stable oral leflunomide 10-20 mg/day for at least 4 weeks.
- •(7)systemic lupus erythematosus : Diagnosis of systemic lupus erythematosus according to the SLE classification criteria of the 2019 EULAR/ACR; History of systemic lupus erythematosus for at least 6 months prior to screening and active disease for 2 months after use of standard treatment regimens prior to screening; BILAG-2004 assesses the presence of at least 1 Grade A or 2 Grade B organ scores; Positive antinuclear antibody, or positive anti-ds-DNA antibody, or positive anti-Sm antibody; SLEDAI-2000 score ≥8 during the screening period.
- •(8)Sjögren's syndrome : Diagnosis of Sjögren's syndrome according to the 2002 International Classification of Primary Sjögren's Syndrome or the 2016 ACR/EULAR classification criteria; Diagnosed with pSS-TP and platelet count < 30×10^9/L; Sjögren's syndrome Disease Activity Index (ESSDAI) score ≥5 during the screening period; Sjögren's syndrome for at least 6 months prior to screening and active disease 2 months after use of conventional treatment regimens prior to screening. Use of immunomodulatory drugs for more than 6 months.
- •(9)systemic sclerosis : Diagnosis of systemic sclerosis according to the 2013 ACR classification criteria for systemic sclerosis. Positive antinuclear antibody at screening. Presence of clear evidence of HRCT progression. History of systemic sclerosis prior to screening for at least 6 months and active disease for 2 months after use of conventional treatment regimens prior to screening.
排除标准
- •(1) Clinically significant central nervous system diseases or pathological changes not caused by the disease itself before screening, including but not limited to: stroke, stroke, aneurysm, epilepsy, convulsions, aphasia, severe head injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or mental disorder.(2) Those with relatively serious heart disease, such as angina, myocardial infarction, heart failure and arrhythmia.(3) History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation.(4) Vaccination, B-cell targeted therapy within 4 weeks prior to screening.(5) History of any malignant neoplastic disease.(6) Patients with end-stage renal failure.(7) The presence or suspicion of uncontrollable fungal, bacterial, viral, or other infections.(8) History of severe allergy to drugs used in clinical studies or raw and excipient materials of experimental drugs, such as cyclophosphamide, fludarabine, DMSO, etc.(9) Patient has active HBV infection or HCV antibody positivity or HIV antibody positivity or syphilis positivity or CMV DNA positivity or EBV DNA positivity.(10) Pregnant or lactating females, or planning to become pregnant within 2 years after reinfusion of the trial drug; The partner of the male patient plans to become pregnant within 2 years of receiving the trial drug.(11) Evidence of active tuberculosis infection.(12) Other conditions assessed by the investigator as unsuitable for enrollment.
研究组 & 干预措施
Anti-BCMA and CD19 CART
Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of Anti-BCMA and CD19 CART will be infused on day 0.
干预措施: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis (Drug)
结局指标
主要结局
Adverse events
时间窗: up to 1 years
Total number, incidence and severity of adverse events (AEs) in patients of SCAR02 infusion. The AEs will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.
次要结局
- The change of CAR copy number in peripheral blood was investigated by comparison with baseline(up to 1 years)
- Disease activity was assessed by DAS28(up to 1 years)
- Modified Rodnan Skin Score assesses disease activity in patients(up to 1 years)
- SLEDAI assesses disease activity in patients(up to 1 years)
- BILAG-2004 assesses disease activity in patients(up to 1 years)
- Change from baseline in Physician's Global Assessment of Arthritis (PGA) (VAS)(up to 1 years)
- Change from baseline in ESR(up to 1 years)
- ACR70 response rate(up to 1 years)
- Clinical response for Sjögren's Syndrome(up to 1 years)
- Change from baseline in participant's assessment of pain (VAS)(up to 1 years)
- HAQ health assessment(up to 1 years)
- Change from baseline in CRP(up to 1 years)