Study of Ultra-Fast CD19 CAR-T Therapy for Refractory SLE

NCT07233642 | Recruiting Phase 1 DMC

• 1 other identifier: PBC097
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of ultra-fast autologous CD19-targeted CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Conditions

Systemic Lupus Erythematosus

Keywords

CD19; CAR-T

Outcome Measures

Primary Outcomes (7)

• The safety of CAR-T cell therapy in patients with refractory SLE [Safety]

  Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and other clinical manifestation assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.

  3 months

• The changes from baseline in SLEDAI-2K [efficacy]

  Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K) is from 0 to 105 points. The higher score means the stronger disease activity.

  6 months

• The changes from baseline in PGA [efficacy]

  Physician Global Assessment(PGA) is a continuous visual analogue scale with 0, 1, 2, and 3 scales. "0" indicates no disease activity and "3" indicates the most severe disease activity.

  6 months

• The changes from baseline in BILAG-2004 [efficacy]

  British Isles Lupus Assessment Group Index 2004(BILAG-2004) consists of 8 systems, each of which is classified as A, B, C and D respectively. "A" indicates that the condition is highly active and requires active treatment. "B" indicates that the condition is active and requires close monitoring or symptomatic treatment. "C" indicates a stable condition. "D" indicates that the system is not involved.

  6 months

• The number of patients with SRI-4 response [efficacy]

  The definition of SRI-4 response: SLEDAI-2K ≥ 4-Point improvement; PGA with no worsening (\<0.3-point increase); BILAG 2004 with no new A domain score and no more than 1 new B domain scores.

  3 months

• The number of patients with LLDAS [efficacy]

  The definition of LLDAS: SLEDAI-2K ≤ 4 and no disease activity in major organs (kidneys, central nervous system, heart and lungs), and no vasculitis or fever; no new disease activity symptoms were added compared with previous disease assessments; PGA ≤ 1; irrespective of serology; with permitted use of low-dose glucocorticoids (prednisolone ≤ 7.5 mg/day), and/or stable immunosuppressives and biologics.

  6 months

• The number of patients with DORIS [efficacy]

  The definition of DORIS: SLEDAI-2K = 0 ; PGA) \< 0.5 ; irrespective of serology; with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤ 5 mg/day), and/or stable immunosuppressives and biologics.

  6 months

Secondary Outcomes (11)

• The number of remission of lupus nephritis [efficacy]

  6 months

• The changes of anti-ds-DNA antibody after infusion [efficacy]

  6 months

• The changes of 24h urine protein after infusion [efficacy]

  6 months

• The changes of C3 and C4 after infusion [efficacy]

  6 months

• Cmax of CAR-T cells [PK parameter]

  3 months

Study Arms (1)

CAR-T treatment group

EXPERIMENTAL

This trial was designed as an open, single-arm, single-center, dose-increasing trial.

Biological: CD19 CAR-T cells

Interventions

CD19 CAR-T cells BIOLOGICAL

Three dose groups (1.5×10\^5/kg, 5×10\^5/kg, 10×10\^5/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

CAR-T treatment group

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥ 5 years old, and no gender limitation;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria, and still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod), hydroxychloroquine and at least 2 DMARDs(include cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab) or intolerant to standard treatments;
• SLEDAI-2K score≥8 points;
• The functions of important organs are basically normal:
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram;
• Renal function: eGFR≥30mL/min/1.73m2;
• Liver function: AST and ALT≤3.0 ULN, total Bilirubin (TBIL) in serum ≤2.0×ULN;
• Lung function: no serious lung lesions, SpO2≥92%;
• Meet the standards of leukapheresis or intravenous blood collection, and no contraindication for leukapheresis;
• Negative pregnancy test for female subjects of childbearing age, and agree to take effective contraceptive measures the first year after CAR-T infusion;
• Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

You may not qualify if:

• Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• Severe acute nephritis: patients who have accepted or was undergoing renal replacement therapy within 3 months prior to transfusion; or in the investgator's opinion, patients who is likely to have significant kidney disease within 3 moths of the study which need high dose glucocorticoid (prednisone dose≥1mg/kg/day or equivalent amount of other steriod), cyclophosphamide, or mycophenolate mofetil treatment;
• Have a history of congenital heart disease or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); or combined with moderate to massive pericardial effusion, serious myocarditis, etc; or patients with unstable vital signs who need hypertensive drugs;
• Uncontrollable infection, or active infection that requires systemic treatment within 3 months prior to screening;
• Received organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening, or ≥Grade 2 GVHD within 2 weeks prior to screening;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; or positive for human immunodeficiency virus (HIV) antibodies; or syphilis test positive;
• Suffered from macrophage activation syndrome(MAS) within 1 month prior to screening (except for those whose safety risks have been ruled out by the researcher after treatment);
• Received CAR-T treatment (except for those whose safety risks have been ruled out by the researchers after treatment);
• Suffered from active pulmonary tuberculosis at screening;
• Received live vaccine within 4 weeks prior to screening;
• Positive in Blood pregnancy test;
• Previous or concurrent malignancy;
• Patients who participated in other clinical study within 3 months prior to screening;
• Any other conditions that the investigators deem it unsuitable for the study.

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jianhua Mao, MD

  Children's Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianhua Mao, MD

CONTACT

13516819071; maojh88@zju.edu.cn

Xue He

CONTACT

15088688407; hexue1119@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Treatment of patients with refractory systemic lupus erythematosus using ultra-fast CD19-targeted CAR-T cells

Study Record Dates

• First Submitted: September 28, 2025
• First Posted: November 18, 2025
• Study Start: November 1, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)