Idiopathic Inflammatory Myopathies, IgG4 Related Disease, Primary Sjögren Syndrome, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Brief summary
Main purpose: To evaluate the safety of UTAA09 injection in the treatment of relapsed/refractory (R/R) autoimmune disease (AID). Secondary purpose: 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.
Detailed description
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, the therapeutic efficacy was evaluated at the frequency of 14d, 28d, 2m, 4m, 6m, 8m, 10m, 12m, 15m, 18m, 21m, 24m after cell transfusion until disease progression (PD), new anti-disease therapy, death, intolerable toxicity, investigator decision, or subject's voluntary withdrawal. Whichever comes first.
Interventions
Intravenous administration, 1 bag each time (depending on individual differences), dose: 1×108-1×109 CD19-CAR-gdT (UTAA09 injection), the investigator can decide whether to reduce or increase the dose and whether multiple infusions are required according to the condition of the subject.
Sponsors
PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
UTAA09 injection
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(2) Expected survival time ≥3 months; (3) Subjects with recurrent/refractory autoimmune diseases who have failed standard treatment or lack effective treatment, Including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, IGG4-associated diseases, primary Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc. (3) Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction. (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.
Exclusion criteria
1. 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; 2. 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; 3. 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; 4. Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment; 5. Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration; 6. 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; 7. Patients who received CAR-T therapy or other gene-modified cell therapy before screening; 8. Participated in other clinical studies 1 month before screening; 9. Evidence of central nervous system invasion during subject screening; 10. Mental patients with depression or suicidal thoughts; 11. Those who received live vaccine within 28 days prior to screening; 12. Situations considered unsuitable for inclusion by other researchers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first) | The maximum amplified concentration (Cmax) of UTAA09 injection in peripheral blood after administration, the time to reach the maximum concentration (Tmax), and the area under the curve AUC0-28d at 28 days and the area under the curve AUC0-90d at 90 days |
| CD19-positive cells | 3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first) | The content of CD19-positive cells in peripheral blood after UTAA09 injection administration: the proportion and absolute value of CD19-positive cells in peripheral blood at each time point; Concentration levels of CAR-T-associated serum cytokines. |
| Disease remission/response/improvement rates | 3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first) | Disease remission/response/improvement rates at 28 days, 2 months, and 3 months after administration. |
| anti-CAR antibody | 3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first) | The positive rate of human anti-CAR antibody at each time point. |
Countries
China
Contacts
Primary Contactsonglou yin, master
Backup Contactdongmei zhou, doctor
Outcome results
None listed