Preliminary Clinical Study of UTAA09 Injection in the Treatment of Relapsed/Refractory Autoimmune Diseases

Early Phase 1

Not yet recruiting

• Conditions: Immune Thrombocytopenia; Systemic Lupus Erythematosus; Idiopathic Inflammatory Myopathies; Sjogren's Syndrome; Rheumatoid Arthritis; Primary Biliary Cholangitis; Systemic Sclerosis
• Interventions: Biological: T cell injection targeting CD19 chimeric antigen receptor

• Registration Number: NCT06417398
• Lead Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.

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

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-27
• Study First Submitted QC: 2024-05-12
• Last Update Submitted: 2024-05-12
• Study Start: 2024-05-14
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16
• Primary Completion: 2024-12-01
• Study Completion: 2025-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T cell injection targeting CD19 chimeric antigen receptor	T cell injection targeting CD19 chimeric antigen receptor	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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