NCT06333483进行中（未招募）1 期
A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 12
- 主要终点
- Adverse events
研究概览
简要总结
This is a Phase 1 study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.
详细描述
This is a single-arm, open-label Phase 1 Study to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe, refractory SLE. Up to a maximum of 18 patients will be treated in a maximum of 3 dose levels.
By using the Bayesian Optimal Interval (BOIN) design for overdose control, the Sponsor will review the Safety Review Committee (SRC) and Independent Data Monitoring Committee (IDMC) recommendation and determine if a dose level is suitable for a subsequent study.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Key Inclusion Criteria-
- •Women or men ≥ 18 years at screening [Spain only] or patients 12 to 65 years of age (inclusive) at the time of signing the informed consent [UK only]
- •Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus
- •Positive for at least one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥ 1:80, or anti-dsDNA (≥ 30 IU/mL) or anti-Smith (> upper limit of normal [ULN]), anti-histone or anti-chromatin (> ULN)
- •Severe, refractory SLE
排除标准
- •Key Exclusion Criteria-
- •Medications
- •Within 2 months of leukapheresis: use of anti-CD20 therapy
- •Prior treatment with anti-CD19 therapy (including bispecifics), adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy)
- •Immunization with a live or attenuated vaccine within 2 months of leukapheresis
- •SLE and Autoimmunity:
- •Recurrent neuropsychiatric lupus or active, severe or unstable neuropsychiatric lupus within 2 years from screening
- •Diagnosis of drug-induced SLE rather than idiopathic SLE
- •Any acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, making the patient ineligible for CD19 CAR T therapy as judged by the Investigator or Sponsor
- •Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the patient
- •Diagnosis of another non-SLE autoimmune disease (e.g., dermatomyositis, polymyositis, scleroderma, rheumatoid arthritis) or overlap syndrome
- •Medical History:
- •History or presence of: (Within 3 months before screening visit)
- •Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, or stroke
- •Evidence of deep venous thrombosis or pulmonary embolism
- •History or presence of severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
- •Clinically significant, uncontrolled heart disease not due to SLE (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled cardiac arrhythmia, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless the patient has a pacemaker) or a recent (within 12 months of screening) cardiac event
- •Active or uncontrolled fungal, bacterial, viral (including COVID-19), or other infection requiring systemic antimicrobials for management
- •Active or latent hepatitis B or active hepatitis C
- •Human immunodeficiency virus, human T-cell leukemia virus (HTLV)-1, HTLV-2 or syphilis positive test at screening
- •History of malignant neoplasms unless disease free for at least 24 months (basal cell or squamous cell carcinoma in situ, or in situ breast cancer on hormonal therapy allowed)
- •History of heart, lung, kidney, liver transplant or hematopoietic stem cell transplant
- •Pregnancy or lactating
- •Laboratory and Organ Function:
- •Left ventricular ejection fraction < 45% (or < institute's lower limit of normal) confirmed by echocardiogram
- •Oxygen saturation (SpO2) < 90% in the absence of oxygen support
- •B cell aplasia
研究组 & 干预措施
AUTO1
Experimental
干预措施: Obecabtagene autoleucel (obe-cel) (Biological)
结局指标
主要结局
Adverse events
时间窗: Up to Month 12
Adverse event (AE) type, frequency, severity, and relationship with obe-cel and lymphodepletion of AEs
Dose-limiting toxicities
时间窗: Up to 28 days from obe-cel infusion
Percentage of patients receiving obe-cel who experience dose-limiting toxicities (DLTs)
Adverse events
时间窗: Up to Month 12
Adverse event (AE) type, frequency, severity, and relationship with obe-cel and lymphodepletion of AEs
次要结局
- Remission rate according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Response over time according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Time to response according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(Up to Month 12)
- Change over time in Physician's global assessment (PGA)(Up to Month 12)
- Remission rate according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Response over time according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Time to response according to Definition of Remission in SLE (DORIS)(Up to Month 12)
- Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(Up to Month 12)
- Change over time in Physician's global assessment (PGA)(Up to Month 12)
- Pharmacokinetics (maximum serum concentration [Cmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood(Up to Month 12)
- Pharmacokinetics (time to reaching maximum serum concentration [Tmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood(Up to Month 12)
- Pharmacokinetics (area under the curve [AUC]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood(Up to Month 12)
- Pharmacokinetics (last observed quantifiable concentration [Clast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood(Up to Month 12)
- Pharmacokinetics (time to reach last observed quantifiable concentration [Tlast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood(Up to Month 12)
- Pharmacodynamics: B cell aplasia(Up to Month 12)
研究者
研究点 (12)
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