Chimeric Antigen Receptors T Cells for Refractory/Recurrent Lupus Nephritis in Children (CAR-T)

An Exploratory Clinical Study of the Safety and Efficacy of CAR-T in Children With Refractory/Recurrent Lupus Nephritis Disease

The goal of this prospective, open, single-arm clinical trial was to evaluate the safety and potential efficacy of CAR T cell therapy in children with refractory/recurrent lupus nephritis. The persistence and cell phenotype of CAR-T cells in vivo and CAR-T treatment-related inflammatory factors were evaluated after treatment. To explore new therapeutic methods, in order to reduce the side effects of traditional therapeutic drugs, increase curative effect, and finally make patients obtain long-term survival and improve survival quality.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Biological: Low-dose CAR-T cells group; Biological: High-dose CAR-T cells group

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xia Gao, M.D.; Phone Number: 86+020-81330569; Email: gaoxiagz@vip.163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Guangzhou Women and Children Medical Center
      • Contact: Xia Gao, M.D.; Phone Number: 86+020-81330569; Email: gaoxiagz@vip.163.com
      • Principal Investigator: Xia Gao

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 6-18 years old (including critical value);
2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;
3. According to the 2018 ISN/RPS LN standards diagnosed with active Class III or IV LN, with or without a membranous component and the biopsy must be performed within 6 months prior to screening;
4. SLEDAI-2000 score ≥8 points;

5. Meeting the diagnosis of refractory lupus nephritis,

   1. defined as treatment with two or more immunosuppressants (including glucocorticoids, cyclophosphamide, tacrolimus, mycophenolic acid analogues, leflunomide, and cyclosporine) for more than 6 months without inducing remission or relapse after remission,
   2. accompanied by proteinuria without remission;
6. Positive expression of CD19 in peripheral blood B cells determined by flow cytometry;
7. Participants had good venous access, no contraindications for cell collection;
8. Participants and their guardians sign the informed consent, understand the study procedures and participate in the clinical study voluntarily;

9. The functions of important organs are basically normal:

   1. Hematopoietic function (blood routine should meet):

      • Lymphocyte count ≥1×109/L,
      • White blood cell count ≥3×109/L,
      • Neutrophil count ≥1×109/L (no colony-stimulating factor treatment within 2 weeks prior to examination),
      • Hemoglobin ≥60g/L;

   2. Liver function:

      • ALT≤3×ULN (except elevated ALT caused by inflammatory myopathy),
      • AST≤3×ULN (except for elevated AST caused by inflammatory myopathy),
      • TBIL≤1.5×ULN (except Gilbert syndrome, total bilirubin ≤3.0×ULN);
   3. Renal function: eGFR ≥30 ml/(min.1.73m2) (Schwartz formula, except abnormal renal function by SLE);

   4. Coagulation function:

      • International standardized ratio (INR) ≤1.5×ULN,
      • prothrombin time (PT) ≤1.5×ULN;
   5. Heart function: hemodynamic stability;
10. Anti-nuclear antibody (ANA) ≥1:80;
11. Eastern Cancer Cooperation Group (ECOG) physical status score 0 to 2.

Exclusion Criteria:

1. Received kidney transplant previously;
2. Serious drug allergy history or allergy;
3. Presence or suspicion of fungal, bacterial, viral or other infections that cannot be controlled or require treatment;
4. Complicated with severe organ dysfunction of heart, liver, lung or coagulation dysfunction;
5. Complicated with congenital immunoglobulin deficiency;

6. Participants with infectious diseases:

   1. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBc Ab) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range;
   2. Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range;
   3. Human immunodeficiency virus (HIV) antibody positive;
   4. Syphilis positive;
7. Diagnosed with malignant tumors in the last five years.
8. Suffer from severe central nervous system disease, mental illness and severe cognitive dysfunction;
9. Participated in other clinical trials within 3 months before enrollment;
10. Received CAR-T therapy previously;
11. Other situations that the researcher considers unsuitable for inclusion.

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: CAR-T; Children who met the inclusion criteria were given transfusions of CAR-T cells

Biological: Low-dose CAR-T cells group; This group of patients received low dose novel structure of Chimeric Antigen Receptors T (CAR-T) cells therapy with an infusion dose of approximately 5×100,000 cells/Kg.; Biological: High-dose CAR-T cells group; This group of patients received high dose novel structure of Chimeric Antigen Receptors T (CAR-T) cells therapy with an infusion dose of approximately 1×1000,000 cells/Kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with CAR-T cells treatment-related adverse events(AE)	Incidence and severity of treatment-related AE, including adverse event of special interest (AESI), as assessed by CTCAE v5.0.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall renal response (ORR) rete	ORR rate: Number of participants meet the complete renal response (CRR) or partial renal response (PRR) as a percentage of total participants. Follow-up for 2 years after CAR-T cells reinfusion, monitored and recorded ORR at study set time points (Month 3, Month 6, Month 12, Month 24, or participant withdrawal from the study).	2 years
Number of participants with SRI-4 response	Number of participants with SLE response Index 4(SRI-4) response: including Systemic Lupus Erythematosus Disease Activity Index(SLEDAI) 2000 scores decreased by ≥4 points from baseline, PGA with no worsening (VAS increased by <0.30 points from baseline), British Isles Lupus Assessment Group(BILAG) 2004 with no new A domain score and no more than 1 new B domain scores. Follow-up for 2 years after CAR-T cells reinfusion, monitored and recorded SRI-4 response at study set time points (Month 3, Month 6, Month 12, Month 24, or participant withdrawal from the study).	2 years

Collaborators and Investigators

• Sponsor: Guangzhou Women and Children's Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: [2025]040A01

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