Idiopathic Inflammatory Myopathies, Immune Thrombocytopenia, Primary Biliary Cholangitis, Rheumatoid Arthritis, Sjogren's Syndrome, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Brief summary
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.
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, 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
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
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 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.
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 |
|---|---|---|
| Peak Plasma Concentration (Cmax） | 3 months after cell reinfusion disease progression/recurrence or start of new anti-disease therapy (whichever occurs first) | UTAA09 injection was administered in peripheral bloodCmax |
| Area under the plasma concentration versus time curve (AUC) | 3 months after cell reinfusion/28d after cell reinfusion | UTAA09 injection was administered in peripheral blood |
| Content of CD19 positive cells in peripheral blood | every visits after infusion up to 2 years | The proportion and absolute value of CD19 positive cells in peripheral blood at each time point |
Contacts
Primary Contactjian wu, Doctor
Outcome results
None listed