Safety and Efficacy of Universal CAR-T Cells (UWD-CD19) Combined with Immunosuppressants in the Treatment of Refractory Autoimmune Diseases

NCT06821659 | Not Yet Recruiting Phase 1

• 1 other identifier: M20250037
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

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, Sjögren's syndrome, systemic sclerosis, inflammatory myopathies, ANCA-associated vasculitis. 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. Clinical studies are exploring the use of CD19-targeting CAR-T cells for the treatment of autoimmune diseases, and their therapeutic efficacy has been demonstrated. In this study, we investigate the safety and efficacy of universal CD19-targeting CAR T cells in the treatment of autoimmune diseases.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety of UWD-CD19 cell injection in the treatment of refractory autoimmune diseases.

  In this study, adverse events (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)

  0-6 months

• Maximum tolerated dose of UWD-CD19 cells

  Dose-limiting toxicity after cell infusion

  28 days

Secondary Outcomes (17)

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

  90 days, 180 days, 360 days

• Low Lupus Disease Activity State(LLDAS)

  90 days, 180 days, 360 days

• Systemic Sclerosis Combined Response Index (CRISS) response

  90 days, 180 days, 360 days

• Modified Rodnan Skin Score (mRSS)

  90 days, 180 days, 360 days

• Vasculitis disease activity assessment (BVAS score)

  90 days, 180 days, 360 days

Study Arms (1)

anti-CD19 CAR-T (UWD-CD19)

EXPERIMENTAL

Biological: anti-CD19 CAR-T cells

Interventions

anti-CD19 CAR-T cells BIOLOGICAL

UWD-CD19

anti-CD19 CAR-T (UWD-CD19)

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.
• \>40kg.
• 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:

• Subjects with a history of alcohol abuse or substance abuse within the past 24 weeks;
• Subjects with other psychiatric disorders such as schizophrenia or major depressive disorder;
• Subjects with a history of malignancies other than B-cell lymphoma;
• Subjects with overlapping diseases that affect the assessment of disease activity;
• Subjects with infections such as human immunodeficiency virus (HIV), hypogammaglobulinemia, T-cell deficiency virus infection, or chronic hepatitis B or C;
• Subjects with known active tuberculosis (TB) infection or bacterial infections;
• Subjects with a history of myocardial infarction, cardiac angioplasty or stent placement, unstable angina, active arrhythmia, or other clinically significant heart diseases within 6 months prior to screening;
• Subjects with a history of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
• Subjects with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels ≥3×ULN, or bilirubin \>1.5×ULN, excluding abnormalities caused by theautoimmune disease;
• Subjects with chronic kidney failure stage 4 or above, defined as an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m² or serum creatinine \>2.5 mg/dL;
• At the screening visit, subjects with any of the following significant hematologic abnormalities caused by bone marrow suppression, excluding abnormalities due to the autoimmune disease:
• Hemoglobin \<70 g/L;
• Absolute neutrophil count \<500/mm³;
• Platelet count \<50,000/mm³;
• Subjects with a history of severe adverse reactions to cyclophosphamide or fludarabine;

Sponsors & Collaborators

• Peking University Third Hospital: lead

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye 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 12, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 12, 2025

Record last verified: 2025-02