Anti-CD19-CD3E-CAR-T Cells in Relapsed/Refractory Autoimmune Disease

NCT06373081 | Recruiting DMC

• 1 other identifier: CD19-CD3E-CN-A1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the safety and efficacy of anti-CD19-CD3E-CAR-T cells in the relapse or refractory autoimmune diseases.

Conditions

Systemic Lupus Erythematosus (SLE); Sjogren's Syndrome; Systemic Sclerosis; Inflammatory Myopathy; ANCA Associated Vasculitis; Antiphospholipid Syndrome

Outcome Measures

Primary Outcomes (8)

• The incidence of dose-limiting toxicities (DLTs) (Safety)

  Safety assessments, including the incidence of dose-limiting toxicities (DLTs) in patients receiving CAR-T cells, are conducted using the NCI-CTCAE version 5.0 standards.

  Up to 28 days from CAR-T infusion

• Proportion of patients for whom the desired dose of anti-CD19-CD3E-CAR-T cells can be successfully manufactured

  Proportion of patients for whom the desired dose of anti-CD19-CD3E-CAR-T cells can be successfully manufactured

  Up to 21 days from apheresis

• Clinical response for relapsed/Refractory SLE

  SLE Response Index 4 (SRI-4) response: Min/Max Value: Not specified; a decrease in score indicates improvement; higher scores indicate worse outcome.

  12 weeks post CAR-T infusion

• Clinical response for Sjögren's Syndrome

  Sjögren's tool for assessing response (STAR): Min/Max Value: Not specified; a decrease in score indicates improvement; higher scores indicate worse outcome.

  12 weeks post CAR-T infusion

• Clinical response for relapsed/refractory/progressive systemic sclerosis

  Composite Response Index in Systemic Sclerosis (CRISS): Min/Max Value: 0 to 1 (expressed as a probability); closer to 1 indicates a better response; higher scores indicate better outcome.

  12 weeks post CAR-T infusion

• Clinical response for relapsed/refractory/progressive inflammatory myopathy

  Total Improvement Score (TIS):Min/Max Value: Not specified; an increase in score indicates improvement; higher scores indicate better outcome.

  12 weeks post CAR-T infusion

• Clinical response for relapsed/refractory anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis:

  Birmingham vasculitis activity score (BVAS) score:Min/Max Value: 0 to 63; an increase in score indicates worsening condition; higher Scores Indicate: Worse Outcome.

  12 weeks post CAR-T infusion

• Clinical response for relapsed/refractory/Catastrophic Antiphospholipid Syndrome

  Evaluation of new thrombosis as an indicator of relapsed/refractory/catastrophic Antiphospholipid Syndrome; higher scores Indicate worse outcome (indicates progression of the syndrome).

  12 weeks post CAR-T infusion

Study Arms (1)

Anti-CD19-CD3E-CAR-T Cells treatment

EXPERIMENTAL

Anti-CD19-CD3E-CAR-T cells, Autologous T-cells expressing a chimeric antigen receptor directed to CD19.

Biological: Anti-CD19-CD3E-CAR-T cells

Interventions

Anti-CD19-CD3E-CAR-T cells BIOLOGICAL

The injection of anti-CD19-CD3E chimeric antigen receptor T (CAR-T) cells, referred to as anti-CD19-CD3E-CAR-T cells. The anti-CD19-CD3E-CAR protein is composed of a murine-derived CD19 single-chain variable fragment (scFv) FMC63, CD28 hinge and transmembrane regions, the intracellular domain of CD3E, the intracellular domain of CD28, and the intracellular domain of CD3ζ, all linked in sequence.

Anti-CD19-CD3E-CAR-T Cells treatment

Eligibility Criteria

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

You may qualify if:

• Age between 18 and 65 years old (inclusive), regardless of gender.
• Positive expression of CD19 on peripheral blood B cells confirmed by flow cytometry.
• Functional requirements for major organs are as follows: 1) Bone marrow function must meet: A. Neutrophil count ≥ 1×109/L (no colony-stimulating factor treatment within 2 weeks before examination); B. Hemoglobin ≥ 60g/L; 2) Liver function: Alanine aminotransferase (ALT) ≤ 3×ULN (excluding ALT elevation due to inflammatory myopathy), aspartate aminotransferase (AST)≤3×Upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy), TBIL≤1.5×ULN (or ≤ 3.0×ULN for subjects with Gilbert syndrome); 3) Renal function: creatinine clearance rate (CrCl) ≥ 30ml/minute (calculated by Cockcroft/Gault formula, acute CrCl decrease due to the target disease is excluded); 4) Coagulation function: International standardized ratio (INR) \<1.5×ULN, prothrombin time (PT) \<1.5×ULN; 5) Cardiac function: Stable hemodynamic.
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• Refractory/Relapsed SLE:
• SLE fulfilling the 2019 the American College of Rheumatology (ACR) /European League Against Rheumatism (EULAR) and classification criteria.
• Systemic lupus erythematosus disease activity index (SLEDAI)-2000 score ≥ 6 with at least one BILAG (British Isle Lupus Rating Group Index 2004) A or two BILAG B; or SLEDAI-2000 score ≥ 8.
• Definition of relapsed/refractory: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids and cyclophosphamide, and any one or more of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc.
• Refractory/Relapsed Sjogren's syndrome:
• Primary Sjogren's syndrome fulfilling the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria.
• EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ≥ 6
• Positive anti-SSA/Ro antibodies
• Definition of relapsed/refractory: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids and cyclophosphamide, and any one or more of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc.
• Refractory/Relapsed/Progressive Systemic Sclerosis:

You may not qualify if:

• Subjects with a history of severe drug allergies or allergic tendencies;
• Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections;
• Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis);
• Subjects with insufficient cardiac function;
• Subjects with congenital immunoglobulin deficiencies;
• History of malignancy within five years;
• Subjects with end-stage renal failure;
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA \>ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing;
• Subjects with psychiatric disorders and severe cognitive impairments;
• Subjects who have participated in other clinical trials within the past 3 months prior to enrollment;
• Subjects who have received biologics with therapeutic effects for indications within 4 weeks prior to enrollment;
• Subjects who have received immunosuppressive agents with therapeutic effects for indications within 2 weeks prior to enrollment;
• Subjects who have received \>10mg/d prednisone or equivalent dose of other steroids within 2 weeks prior to enrollment;
• Pregnant women or women planning to conceive;
• Completion of Step 1 and successful preparation of CAR-T cell product;

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Shanghai ChangZheng hospital

Shanghai, 200003, China

RECRUITING

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System 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; Skin Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Study Officials

• Huji Xu, Ph.D, MD

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huji Xu, Ph.D, MD

CONTACT

86021-81885514; xuhuji@smmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician, Head of the Department of Rheumatology and Immunology, Shanghai Changzheng Hospital.

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: April 20, 2024
• Primary Completion: April 15, 2025
• Study Completion: April 15, 2026
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)