Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Moderate to Severe Active SLE Clinical Research

A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Moderate to Severe Active Systemic Lupus Erythematosus

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Metabolically Armed CD19 CAR-T cells

Detailed Description

This is a single arm, open-label study. This study is indicated for moderate to severe active systemic lupus erythematosus. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products and our earlier disclosed clinical trials .

1. Main research objectives: To evaluate the safety and efficacy of metabolically armed CD19 CAR-T Cells in the treatment of moderate to severe active SLE.

2. Secondary research objectives:

1. To evaluate the pharmacokinetic (PK) and pharmacodynamics(PD) characteristics of metabolically armed CD19 CAR-T Cells after infusion and their relationship with the number of B cells.
2. To evaluate the effects of the concentration of autoimmune antibodies and complement after infusion of metabolically armed CD19 CAR-T Cells.
3. To further explore the feasibility and safety of CAR-T therapy regimens without lymphodepletion pretreatment.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Mingming Zhang; Phone Number: 86-13656674208; Email: mingmingzhang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, MD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com
      • Principal Investigator: He Huang, MD
      • Contact: He Huang, MD; Phone Number: 86-13605714822; Email: hehuangyu@126.com
      • Principal Investigator: Yongxian Hu, MD
      • Principal Investigator: Jin Lin, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All subjects or guardians must sign an informed consent form approved by the Ethics Committee in person before commencing any screening process;
• Be over 18 years of age, male or female;
• A diagnosis of SLE according to the 2012 systemic lupus international collaborating clinics(SLICC);

• The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening:

  1. Conventional regimens for SLE are corticosteroids and one or more immunomodulatory drugs over 6 months；

  2. Oral corticosteroids must meet the following requirements:

     • Prednisone (or equivalent) ≥7.5 mg/ day, and ≤60 mg/ day；
     • There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants；
     • At least 8 weeks of treatment prior to screening, and the dose must be kept stable for > 2 weeks.
• Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or anti-Smith antibodies；
• SELENA-SLEDAI score ≥8 during the screening period. Score ≥6 for SELENA-SLEDAI clinical symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or anti-DS-DNA antibody score is present；
• Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo;
• CD19 expression was positive by or flow cytometry ;

• Organ function：

  1. Complete blood count (CBC) test [the following criteria should be met within 24 hours prior to apheresis, and supportive treatment such as transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) should be avoided within 7 days prior to detection]

     • Lymphocyte count ≥ 0.5×109/L (except for those receiving bridging chemotherapy);
     • Platelet count ≥ 25×109/L;
     • Hemoglobin ≥ 70.0 g/L

  2. Blood Biochemistry:

     • Serum creatinine (Scr) ≤ 1.5 x ULN, or
     • endogenous creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault formula);
     • alanine aminotransferase (ALT) ≤ 2.5 x ULN;
     • aspartate aminotransferase (AST) ≤ 2.5 ×ULN;
     • Total bilirubin (TBIL) ≤ 2 ×ULN; Subjects with total bilirubin < 3 × ULN and direct bilirubin < 1.5× ULN with Gilbert-.Meulengracht syndrome could be included;
     • Serum lipase and amylase ≤ 1.5×ULN;
     • Alkaline phosphatase (ALP) ≤ 2.5 ×ULN;
     • In case of bone or liver metastasis, AST, ALT and ALP ≤ 5 ×ULN;
     • Prothrombin time (PT) extended ≤ 4 s, fibrinogen ≥ 1 g/L, activated partial thromboplastin time (APTT) ≤ 1.5 ×ULN;
  3. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) > 91% in indoor air environment..
• Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45％.

Exclusion Criteria:

• Severe lupus nephritis (defined as proteinuria > 6 g/24h or serum creatinine > 2.5 mg/dL or 221 μmol/L), treatment with active nephritis with Prohibited drugs, hemodialysis, or prednisone ≥100 within 8 weeks prior to screening mg/d or equivalent glucocorticoid therapy ≥14 days.
• Prior to screening, other lupus crises, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis.
• Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Combined with other autoimmune diseases, systematic treatment is needed.
• History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
• IgA deficiency was present during screening (serum IgA level < 10 mg/dL).
• Other conditions that the investigator considered should not be enrolled in this clinical study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of Metabolically Armed CD19 CAR-T cells; Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0.	Drug: Metabolically Armed CD19 CAR-T cells; Each subject receive metabolically armed CD19 CAR- T cells by intravenous infusion; Other Names: Meta10-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Determine the Maximal Tolerable Dose(MTD).	MTD will be determined based on DLTs observed during the first 35 days of study treatment.
DCR	Disease control rates (DCR) assessed according to SLEDAI-2000, Physician Overall Assessment (PGA), and medication.	3 and 6 months following infusion of Meta10-19.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of CAR-T cells	Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion.	Up to 12 months after CAR-T treatment.
Pharmacodynamics of CAR-T cells	Concentration levels of CAR-T related serum cytokines such as CRP, IL-6, INF-γ at each time point.	Up to 28 days after infusion.
Autoantibody detection	Concentration levels of B cell related serum antibodies such as complement factor C3 , ANA, anti-dsDNA each time point.	Up to 12 months after CAR-T treatment

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Leman Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 5, 2027

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Meta10-19; CAR-T Cells Therapy
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: Meta10-19-007

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
• product manufactured in and exported from the U.S.: No