Study of Autologous CD19-Targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- The safety of PTOC1 cell therapy in patients with refractory SLE [Safety]
研究概览
简要总结
This is an investigator-initiated trial aimed at assessing the safety and efficacy of PTOC1 cells Injection in the treatment of refractory systemic lupus erythematosus.
详细描述
Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death.
Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients typically need to remain on medication indefinitely. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these treatments cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. In addition, discontinuing these drugs can lead to disease relapse, and patients still face the challenges of lifelong medication and an incurable disease.
CAR-T therapy is an adoptive cell therapy that uses genetic modification technology to reprogram T cells and eliminate target cells expressing disease-related antigens through antigen-specific recognition. Clinical studies have demonstrated that CD19-targeted CAR-T cells hold significant therapeutic potential for SLE. Compared with traditional CAR-T cells, PTOC1 cells Injection, relying on an innovative CAR-T manufacturing system, can be produced in an extremely short period of time (with a preparation time of only 10 minutes).
The purpose of this study is to assess the safety and efficacy of PTOC1 cells Injection in the treatment of refractory SLE.
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 5 years, no gender limitation;
- •Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria, and still in moderate to severe disease activity despite ≥ 3 months of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steroid), combined with hydroxychloroquine, and at least 2 Immunosuppressants or biologics (including cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, belimumab, and rituximab) or intolerant to standard treatments;
- •SLEDAI-2K score ≥ 8 points;
- •The functions of vital organs must meet the following requirements:
- •cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%, with no obvious abnormalities on electrocardiogram (ECG);
- •renal function: eGFR ≥ 30 mL/min/1.73m2;
- •hepatic function: AST and ALT ≤ 3.0×ULN, total bilirubin ≤ 2.0×ULN;
- •pulmonary function: no severe pulmonary lesions; blood oxygen saturation ≥ 92% under non-oxygen supplementation conditions.
- •Meet the criteria of leukapheresis or intravenous blood collection, and no contraindication for leukapheresis;
- •Negative pregnancy test for female subjects of childbearing age, and agree to take effective contraceptive measures until one year after infusion;
- •Participant or his/her guardians agree to participate in the clinical trial and sign the informed consent form indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.
排除标准
- •Central nervous system (CNS) diseases: presence of CNS lupus symptoms requiring intervention within 60 days, including epilepsy, confusion, cerebrovascular events, etc;
- •Congenital heart disease or severe arrhythmia before screening: Including multifocal and frequent supraventricular tachycardia, ventricular tachycardia, etc.; or complicated with moderate to large pericardial effusion, severe myocarditis, etc.; or patients with unstable vital signs who require vasopressors to maintain blood pressure;
- •Presence of active infections requiring systemic treatment or uncontrolled infections within 3 months prior to screening;
- •Having received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; or having grade 2 or above acute graft-versus-host disease (GVHD) within 2 weeks prior to screening;
- •Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA level exceeding the normal range; positive for hepatitis C virus (HCV) antibody with peripheral blood hepatitis C virus (HCV) RNA level exceeding the normal range; positive for human immunodeficiency virus (HIV) antibody; positive for treponema pallidum antibody;
- •History of macrophage activation syndrome within 1 month prior to screening (except for those for whom the investigator has determined that safety risks are excluded after treatment);
- •History of previous CAR-T therapy (except for those for whom the investigator has determined that safety risks are excluded after treatment);
- •Presence of active pulmonary tuberculosis at the time of screening;
- •Having received any vaccination within 4 weeks prior to screening;
- •Positive result of blood pregnancy test;
- •A confirmed diagnosis of malignant diseases such as tumors prior to screening;
- •Participation in other clinical trials within 3 months prior to enrollment;
- •Other circumstances that the investigator deems inappropriate for participation in this study.
研究组 & 干预措施
PTOC1
This trial was designed as an open, single-arm, single-center, dose-exploration trial.
干预措施: PTOC1 (Biological)
结局指标
主要结局
The safety of PTOC1 cell therapy in patients with refractory SLE [Safety]
时间窗: 3 months
Types, frequency and severity of adverse events.
The changes in SLEDAI-2K from baseline [efficacy]
时间窗: 6 months
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ranges from 0 to 105 points. The higher the score, the higher the disease activity.
The changes in PGA from baseline [efficacy]
时间窗: 6 months
Physician Global Assessment(PGA) is a continuous visual analogue scale with 0, 1, 2, and 3 scores. "0" indicates no disease activity and "3" indicates the most severe disease activity.
The changes in BILAG-2004 from baseline [efficacy]
时间窗: 6 months
British Isles Lupus Assessment Group Index 2004(BILAG-2004) consists of 8 systems, each of which is graded as A, B, C and D. "A" indicates that the condition is highly active and requires active treatment. "B" indicates that the condition is active and requires close monitoring or symptomatic treatment. "C" indicates a stable condition. "D" indicates that the system is uninvolved.
The number of patients with SRI-4 response [efficacy]
时间窗: 3 months
The definition of SRI-4 response: SLEDAI-2K ≥ 4 points improvement; PGA \<0.3 points increase; BILAG 2004 with no new A grade score and no more than 1 new B grade score.
The number of patients with LLDAS [efficacy]
时间窗: 6 months
The definition of LLDAS: SLEDAI-2K ≤ 4 points and no disease activity in major organs (kidney, central nervous system, heart and lung), and no vasculitis or fever; no new disease activity symptoms compared with previous disease assessments; PGA ≤ 1; serological parameters not required; with the permitted use of low-dose glucocorticoids (prednisolone ≤ 7.5 mg/day), and/or stable immunosuppressives and biologics.
The number of patients with DORIS [efficacy]
时间窗: 6 months
The definition of DORIS: SLEDAI-2K = 0 points; PGA \< 0.5 points; serological parameters not required; with the permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤ 5 mg/day), and/or stable immunosuppressives and biologics.
次要结局
- Cmax of PTOC1 cells [PK parameter](3 months)
- Tmax of PTOC1 cells [PK parameter](3 months)
- AUC28d/90d of PTOC1 cells [PK parameter](3 months)
- The degree of B cell depletion [PD parameter](3 months)
- The concentration of IL-6 [PD parameter](3 months)
- The concentration of CRP [PD parameter](3 months)
- The concentration of ferritin [PD parameter](3 months)
- The proportion of major B-cell subtypes(6 months)
- The correlation between the proportion of major B-cell subtypes and the reduction of disease activity(6 months)