A Phase 1b, Open-label, Multi-cohort Study of AZD0120, an Autologous CD19/BCMA Targeting Chimeric Antigen Receptor T-cell, in Adults With Autoimmune Diseases
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 27
- 试验地点
- 20
- 主要终点
- Number of participants and severity of dose limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs)
概览
简要总结
This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA).
详细描述
This is a Phase 1b, open-label, multi-center, multi-cohort clinical study of AZD0120, a CD19/BCMA dual CAR T-cell therapy, to evaluate the safety in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA) for determination of the recommended phase 2 dose for each disease cohort. Approximately 9-12 participants will be evaluated per disease cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent.
- •Adequate physiological function and reserve at screening.
- •Able to comply with recommended medication washout period.
- •Participants who are suitable for the study as determined by medical evaluation and at the discretion of the investigator.
- •Willingness to remain on/start appropriate, highly effective methods of birth control or other acceptable criteria.
排除标准
- •BMI at screening \< 18 or \> 35kg/m
- •Any prior CAR T exposure.
- •Unable or unwilling to remain within proximity (\~2 hours travel time) of the administering investigational site for the first 28 days post study drug administration.
- •Received a bone marrow or solid organ transplant at any time or on an active transplant waiting list.
- •Received any investigational drug within ≥ 5 half-lives or 4 weeks, whichever is longer, prior to screening.
- •Has certain heart conditions that could make it unsafe or unsuitable to take part in the study.
- •Requirement for supplemental oxygen at rest (except at night for sleep apnea) or mechanical ventilation.
- •Uncontrolled hypertension (\> 160/100 mmHg) or symptomatic hypertension.
- •Any central nervous system disease that may impact participants safety in the investigator's opinion.
- •Other concurrent autoimmune or autoinflammatory disease. Certain autoimmune/autoinflammatory diseases may be included after discussion with the medical monitor.
研究组 & 干预措施
AZD0120 Regimen 1
Participants will receive an infusion of AZD0120 Regimen 1.
干预措施: AZD0120 (Biological)
AZD0120 Regimen 2
Participants will receive an infusion of AZD0120 Regimen 2.
干预措施: AZD0120 (Biological)
结局指标
主要结局
Number of participants and severity of dose limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs)
时间窗: 1 year
Incidence and severity of DLTs and TEAEs to evaluate the safety of AZD0120 and to confirm the recommended Phase 2 dose (RP2D) in each indication SSc, IIM, or RA
次要结局
- Cellular Kinetics - Tmax(1 year)
- Cellular Kinetics - AUC(1 year)
- Cellular Kinetics - t½λz(1 year)
- Cellular Kinetics - Cmax(1 year)
- Cellular Kinetics - Clast(1 year)
- Cellular Kinetics - Tlast(1 year)
- Cellular Kinetics - AUClast(1 year)
- Anti-drug antibodies (ADA) developed against AZD0120 from baseline(1 year)
- Proportion of participants with detectable replication competent lentivirus (RCL) at pre-specified post infusion timepoints.(1 year)
- Change from baseline in the Disease Activity Score (DAS) 28-C-reactive protein (CRP). The DAS28-CRP is a measure from 0-10 with higher scores indicating greater disease activity.(1 year)
- Change from baseline in modified Rodnan Skin Score (mRSS). The mRSS is a measure of skin thickness with a range of 0-51 with higher scores indicating more severe disease.(1 year)
- Change from baseline in the total improvement score (TIS). The TIS ranges from 0-100 with higher scores indicating greater improvement.(1 year)