Preliminary Clinical Study of UTAA09 Injection in the Treatment of Relapsed/Refractory Autoimmune Diseases
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 10
- 主要终点
- AE
研究概览
简要总结
To evaluate the safety of UTAA09 injection in the treatment of relapsed/refractory (R/R) autoimmune disease (AID).
To evaluate the pharmacokinetic (PK) profile of UTAA09 injection in patients with R/R AID.
To evaluate the pharmacodynamic (PD) characteristics of UTAA09 injection in patients with R/R AID.
To evaluate the initial efficacy of UTAA09 injection in the treatment of R/R AID subjects.
To evaluate the immunogenicity of UTAA09 injection in R/R AID subjects.
详细描述
This clinical trial was designed as a single-arm, open-label, single-center, investigator-initiated early-stage clinical study to evaluate the safety of UTAA09 injection in patients with relapsed/refractory AID. After signing the informed consent letter, qualified subjects were screened for infusion of UTAA09 injection, and their blood was collected before and after infusion for pharmacokinetics, pharmacodynamics, immunogenicity, safety and other evaluation. In addition to the baseline period, therapeutic efficacy was evaluated at a frequency of 28d, 2m, 3m, 4m, 5m, 6m, 8m, 10m, 12m after cell transfusion, and tumors were evaluated until disease progression (PD), new anti-disease therapy, death, intolerable toxicity, investigator decision, or subject's voluntary withdrawal, whichever occurred first.
All adverse events were recorded from the beginning of the subject's elutriation pre-treatment (if it occurred) until 3 months after the subject received cell transfusion or disease progression/recurrence or initiation of a new anti-disease therapy or the end of the study, whichever occurred first, and 3 months after cell transfusion or disease progression/recurrence or initiation of a new anti-disease therapy (whichever occurred first) until the end of the study. Only adverse events associated with the study product were collected
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(2) Expected survival time ≥3 months; (3) Subjects with recurrent/refractory autoimmune disease who have failed standard treatment or lack effective treatment, including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc.
- •(4) Liver and kidney function, cardiopulmonary function meet the following requirements:
- •Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
- •Blood oxygen saturation >91% in non-oxygen state;
- •Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
- •(5) no serious mental disorders; (6) Can understand this test and have signed the informed consent.
排除标准
- •Malignant tumors other than R/R AID disease in the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
- •Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
- •Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
- •Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
- •Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
- •Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
- •Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
- •Participated in other clinical studies 1 month before screening;
- •Evidence of central nervous system invasion during subject screening;
- •Mental patients with depression or suicidal thoughts;
- •Those who received live vaccine within 28 days prior to screening;
- •Situations considered unsuitable for inclusion by other researchers.
结局指标
主要结局
AE
时间窗: 3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)
Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities according to the Common Adverse Event Evaluation Standard NCI CTCAE version 5.0.
次要结局
- Peak Plasma Concentration (Cmax）(3 months after cell reinfusion disease progression/recurrence or start of new anti-disease therapy (whichever occurs first))
- Area under the plasma concentration versus time curve (AUC)(3 months after cell reinfusion/28d after cell reinfusion)
- Content of CD19 positive cells in peripheral blood(every visits after infusion up to 2 years)