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

Early Clinical Study of UTAA09 Injection in the Treatment of Relapsed/Refractory

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus; Systemic Sclerosis; Idiopathic Inflammatory Myopathies; Primary Sjögren Syndrome; IgG4 Related Disease
• Intervention / Treatment: Biological: T cell injection targeting CD19 chimeric antigen receptor

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: songlou yin, master; Phone Number: 0516-85806210; Email: yinsonglou@163.com
• Study Contact Backup: Name: dongmei zhou, doctor; Phone Number: 18052268809

Study Locations

• China
  • Hefei, China
    • Recruiting
    • PersonGen.Anke Cellular Therapeutice Co., Ltd
    • Contact: Huimin Meng, doctor; Phone Number: +86-18015580390; Email: huimin.meng@persongen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T cell injection targeting CD19 chimeric antigen receptor; 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	Biological: T cell injection targeting CD19 chimeric antigen receptor; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities according to the Common Adverse Event Evaluation Standard NCI CTCAE version 5.0	3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	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	3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)
CD19-positive cells	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.	3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)
Disease remission/response/improvement rates	Disease remission/response/improvement rates at 28 days, 2 months, and 3 months after administration.	3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)
anti-CAR antibody	The positive rate of human anti-CAR antibody at each time point.	3 months after cell reinfusion or disease progression/recurrence or start of new anti-disease therapy (whichever occurs first)

Collaborators and Investigators

• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Investigators: Principal Investigator: songlou yin, master, The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Muscular Diseases; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Myositis; Immunoglobulin G4-Related Disease; Sjogren's Syndrome
• Other Study ID Numbers: PG-005-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No