A Phase 1b/2 Study of AZD0120, a Chimeric Antigen Receptor T-cell (CAR T) Therapy Targeting CD19 and B-cell Maturation Antigen (BCMA) in Subjects With Refractory Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 150
- 试验地点
- 20
- 主要终点
- PHASE 1B: To evaluate the safety and tolerability of AZD0120 in participants with refractory systemic lupus erythematosus (SLE)
研究概览
简要总结
This is a Phase 1b/2, single-arm, open-label, multi-center, clinical study of AZD0120, a CD19/BCMA dual CAR T cell therapy, to evaluate the safety, tolerability, and efficacy in adult participants with refractory Systemic Lupus Erythematosus.
详细描述
The study will enrol adult participants with refractory Systemic Lupus Erythematosus (SLE) The study will be run in 2 parts;
First part is Phase 1b during which the study aims to assess safety and tolerability of AZD0120 in patients in refractory SLE cohorts
Second part is Phase 2, during which the study aims to assess safety, tolerability and efficacy of the selected dose, following Phase 1b completion, in patients with refractory SLE
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
- •Males or females aged 18 through 70 years inclusive at the time of consent.
- •Written informed consent in accordance with federal, local, and institutional guidelines.
- •Must be able and willing to adhere to the study visit schedule and other protocol requirements
- •Adequate hepatic, renal, pulmonary, and cardiac function
- •Have a clinical diagnosis of SLE according to the EULAR/ American College of Rheumatology (ACR) 2019 criteria with a positive ANA ≥1:80 and a score ≥
- •Have used at least two standard immunosuppressants (including one biological agent).
- •SLEDAI-2K score ≥6 at screening.
- •Must include a significant SLE related organ involvement: arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, vasculitis, or renal.
- •For lupus nephritis: Diagnosis of proliferative lupus nephritis based on a renal biopsy obtained within 6 months prior to signing the informed consent form or during the screening period Class III, IV or V LN according to the WHO 2003 ISN/RPS classification.
排除标准
- •Have received prior treatment with CAR T therapy directed at any target.
- •Have received any therapy that is targeted to CD19 and/or BCMA
- •Received allogenic stem cell transplant or autologous stem cell transplant.
- •An active malignancy that is progressing or requires active treatment.
- •Primary immunodeficiency
- •Active viral or bacterial infection
研究组 & 干预措施
AZD0120
Single dose of AZD0120
干预措施: Fludarabine (Drug)
AZD0120
Single dose of AZD0120
干预措施: AZD0120 (Biological)
AZD0120
Single dose of AZD0120
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
PHASE 1B: To evaluate the safety and tolerability of AZD0120 in participants with refractory systemic lupus erythematosus (SLE)
时间窗: 2 years
The incidence and severity of adverse events (AEs)
PHASE 1B: Recommended Phase 2 Dose (RP2D) of AZD0120 in for Phase 2
时间窗: 2 years
To determine the recommended phase 2 dose (RP2D) of AZD0120
PHASE 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE
时间窗: 2 years
Proportion of participants achieving SRI-4 response
次要结局
- PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE(2 years)
- PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE(2 years)
- PHASE 2: To assess changes from baseline for reported health-related quality of life, overall health status(2 years)
- PHASE 1B & 2: To assess immunogenicity of AZD0120(2 years)
- PHASE 1B & 2: To determine whether replication-competent lentivirus is present in participants that receive AZD0120(2 years)
- PHASE 2: To further characterize the safety of AZD0120 in participants with refractory SLE(2 years)