Safety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases

NCT06828042 | Recruiting Phase 1

• 1 other identifier: M20250025
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Autoimmune diseases refer to a common category of diseases caused by the immune system reacting to self-antigens, leading to tissue damage. Autoimmune diseases encompass a wide variety of conditions, such as systemic lupus erythematosus（SLE）, Sjögren's syndrome (SS), systemic sclerosis (SSc), inflammatory myopathies (IM), ANCA-associated vasculitis (AAV), and antiphospholipid syndrome (APS). They affect the quality of life, while in severe cases, they can be life-threatening. Additionally, they impose a heavy economic burden on society. Current treatments for autoimmune diseases include glucocorticoid, immunosuppressants, and biologics. B cell-driven humoral immune abnormalities are a central pathogenic mechanism in many autoimmune diseases. When autoreactive B cells are excessively activated, they produce large amounts of autoantibodies and immune complexes. These antibodies and immune complexes can cause damage to various tissues and organs, leading to the development of multiple autoimmune diseases. Therefore, targeting B cells to treat autoimmune diseases is an attractive therapeutic strategy. Chimeric Antigen Receptor (CAR)-T cells targeting the B cell surface molecule CD19 have achieved significant clinical progress in acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma, with several CD19 CAR-T therapies approved for marketing worldwide. Increasingly, clinical studies are exploring the use of CD19 CAR-T cells for the treatment of autoimmune diseases, and their therapeutic efficacy has been demonstrated. In this study, the investigators used γδ T cells as carrier cells to investigate the safety and efficacy of universal CAR-γδ T cells in the treatment of autoimmune diseases.

Conditions

Systemic Lupus Erthematosus; Systemic Sclerosis (SSc); Sjogren Syndrome; ANCA Associated Vasculitis (AAV); Inflammatory Myopathies; Antiphospholipid Syndrome

Outcome Measures

Primary Outcomes (2)

• Safety of QH103（anti-CD19 CAR-γδT cells）

  Incidence of Treatment-Emergent Adverse Events (AEs) in this study. AEs are defined as any adverse medical events occurring from the initiation of lymphodepleting chemotherapy to 12 months after the completion of QH103 cell infusion. The incidence, duration, severity, and management of all adverse events occurring after the participants' enrollment will be recorded and evaluated.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Graft-versus-host disease (GVHD) will be graded based on the criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v5.0).

  0-Month 12

• Maximum tolerated dose of CD19 CAR-γδT cells

  Dose-limiting toxicity after cell infusion

  28 days

Secondary Outcomes (17)

• Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) score

  Month 3, 6, 9, and 12

• SRI-4 response

  month 3, 6, 9, and 12

• Sjögren's Tool for Assessing Response (STAR) score

  Month 3, 6, 9, and 12.

• EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

  Month 3, 6, 9, and 12

• EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)

  Month 3, 6, 9, and 12

Study Arms (1)

anti-CD19 CAR-γδ T

EXPERIMENTAL

Biological: anti-CD19 CAR T cell therapy

Interventions

anti-CD19 CAR T cell therapy BIOLOGICAL

anti-CD19 CAR-γδ T cell therapy

anti-CD19 CAR-γδ T

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18-80 years (inclusive), male or female.
• Positive expression of CD19 on peripheral blood B cells by flow cytometry.
• Diagnosed with refractory autoimmune disease, defined as: Ineffectiveness of conventional treatment for more than 6 months, or Disease activity recurrence after remission. Definition of conventional treatment: Use of glucocorticoids and any of the following immunosuppressants or biologics: cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, telitacicept, etc.
• Currently receiving one or more standard therapies at a stable dose, including glucocorticoids, antimalarials, immunosuppressants, or biologics. If the subject is receiving glucocorticoids, the following conditions must be met: During screening and the screening period, the maximum dose of glucocorticoids is 30 mg/day prednisone (or an equivalent dose). The glucocorticoid dose must remain stable for ≥7 days before screening, and during the screening period, the dose adjustment must not exceed \>5 mg/day prednisone (or an equivalent dose). If the subject is receiving antimalarials and/or conventional immunosuppressants: The treatment must have started ≥12 weeks before screening. The medication dose must remain stable for ≥8 weeks before screening and throughout the screening period. Before cell infusion, other immunosuppressants (excluding hydroxychloroquine), including belimumab, telitacicept, CD20 monoclonal antibodies, or other biologic immunosuppressants, must be discontinued for at least 5 half-lives.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must use medically approved contraceptive methods or practice abstinence during the study treatment period and for at least 6 months after the study. Female participants of childbearing potential must have a negative serum HCG test within 7 days before enrollment and must not be breastfeeding.
• Willing to participate in the trial and sign the informed consent form.
• Systemic Lupus Erythematosus (SLE):
• Meets the 2019 EULAR/ACR classification criteria for SLE.
• ANA titer ≥1:80, or positive for anti-dsDNA and/or anti-Sm antibodies.
• Disease activity score (SLEDAI-2000) ≥8.
• Sjögren's Syndrome:
• Meets the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren's syndrome.
• Disease activity score (ESSDAI) ≥5.
• Positive for anti-SSA/Ro antibodies.
• Systemic Sclerosis (SSc):

You may not qualify if:

• History of severe drug allergies or allergic constitution.
• Presence or suspicion of uncontrolled or treatment-requiring fungal, bacterial, viral, or other infections.
• Central nervous system (CNS) diseases caused by autoimmune or non-autoimmune conditions, including epilepsy, psychiatric disorders, organic brain syndrome, cerebrovascular accidents, encephalitis, or CNS vasculitis.
• Dysfunction of major organs not meeting the following criteria (exceptions allowed if abnormalities are caused by autoimmune disease): a. Bone marrow function: White blood cell count ≥3×10⁹/L. Neutrophil count ≥1×10⁹/L (without GSF treatment within 2 weeks prior to testing). Hemoglobin ≥60 g/L. Platelet count ≥50×10⁹/L. b. Liver function: ALT ≤3×ULN (exceptions for ALT elevation caused by inflammatory myopathy). AST ≤3×ULN (exceptions for AST elevation caused by inflammatory myopathy). IBIL ≤1.5×ULN (exceptions for Gilbert's syndrome). Total bilirubin ≤3.0×ULN. c. Renal function: Creatinine clearance (CrCl) ≥30 mL/min (calculated using the Cockcroft/Gault formula, exceptions for acute CrCl decline caused by the disease itself). d. Coagulation function: International normalized ratio (INR) ≤1.5×ULN. Prothrombin time (PT) ≤1.5×ULN. e. Cardiac function: Stable hemodynamics.
• Subjects with congenital immunoglobulin deficiencies.
• History of malignancy within the past five years.
• Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA levels exceeding the detection limit; positive hepatitis C virus (HCV) antibodies with detectable HCV RNA in peripheral blood; positive HIV antibodies; or positive syphilis test results.
• Subjects with psychiatric disorders or severe cognitive impairment.
• Participation in other clinical trials within 3 months prior to enrollment.
• Previous treatment with CAR-T therapy.
• History of severe adverse reactions to cyclophosphamide or fludarabine.
• Any other reason that the investigator determine that subjects cannot be included in this study.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Scleroderma, Systemic; Sjogren's Syndrome; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myositis; Antiphospholipid Syndrome

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Xiaoying Zhang

CONTACT

86+13810001444; zhang_xiaoying@pku.edu.cn

Xiaoying Zhang

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 14, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-04

Locations

CN (1)