Overview
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.
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.
Eligibility
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.