Autologous CD19/BCMA Dual-Target CAR-T for Relapsed/Refractory Autoimmune Diseases

NCT07361094 | Recruiting Phase 1

• 1 other identifier: BJBR-2025-AID-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, leading to chronic inflammation and damage to organs such as the kidneys, lungs, muscles, nerves, or blood cells. Although many treatments are available, some patients do not respond adequately or experience repeated disease flares despite long-term therapy. New treatment approaches are therefore needed for patients with relapsed or refractory autoimmune diseases. This study is an exploratory clinical trial designed to evaluate the safety and potential benefits of a novel cell-based therapy called autologous CD19-BCMA dual-target CAR T-cell therapy. This treatment uses a patient's own immune cells, which are collected from the blood, modified in the laboratory to recognize specific immune cells involved in autoimmune disease, and then infused back into the patient. The study includes adult patients with certain relapsed or refractory autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, inflammatory muscle diseases, Sjögren's syndrome, autoimmune hemolytic anemia, and multiple sclerosis. After cell collection and preparative treatment, participants will receive a single infusion of the investigational CAR T-cell therapy and will be closely monitored for safety. The main purpose of this study is to better understand the safety of this treatment, including possible side effects. The study will also explore how the disease responds to treatment over time. Participants will be followed for up to two years after treatment to assess safety and clinical outcomes. The results of this study may help researchers better understand whether this type of cell therapy could be a feasible treatment option for patients with difficult-to-treat autoimmune diseases in the future.

Conditions

Relapsed/Refractory Systemic Sclerosis; Relapsed/Refractory Idiopathic Inflammatory Myopathies; Relapsed/Refractory sjögren's Syndrome; Relapsed/Refractory Autoimmune Hemolytic Anemia; Relapsed/Refractory Multiple Sclerosis; Relapsed/Refractory Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Number and percentage of participants with adverse events (AEs), serious adverse events (SAEs), laboratory abnormalities, and adverse events of special interest (AESIs: CRS and ICANS), graded per CTCAE v5.0 and ASTCT 2019 criteria

  AEs will be collected from the time of signing the informed consent form through 2 years after CAR-T infusion or the exit visit, whichever occurs first; if disease relapse occurs within 6 months after infusion, AEs will be collected as much as possible through 6 months post-infusion with participant cooperation. All AEs will be coded using MedDRA and summarized by System Organ Class (SOC) and Preferred Term (PT) as the number and percentage of participants with events. AE severity will be summarized using CTCAE v5.0. CRS and ICANS will be summarized using ASTCT 2019 grading criteria. AESIs (including CRS and ICANS) and SAEs (including death) will be listed separately.

  From Day 0 through Month 24 after infusion (including Day 1-28 observation and Month 2-24 follow-up).

Study Arms (1)

Autologous CD19-BCMA Dual-Target CAR T-Cell Therapy (Fixed Dose)

EXPERIMENTAL

The study uses a fixed dose of 1 × 10⁶ CAR-T cells per kilogram of body weight for infusion, followed by a 24-month follow-up period after cell infusion to evaluate safety and efficacy.

Drug: Autologous CD19-BCMA Dual-Target CAR T-Cell Therapy

Interventions

Autologous CD19-BCMA Dual-Target CAR T-Cell Therapy DRUG

Autologous CD19-BCMA dual-target CAR T-cell therapy is a personalized cell-based immunotherapy manufactured from each participant's own peripheral blood T lymphocytes. Following leukapheresis, autologous T cells are genetically modified ex vivo to express a chimeric antigen receptor targeting both CD19 and B-cell maturation antigen (BCMA), enabling recognition and elimination of B-lineage cells and antibody-producing plasma cells implicated in autoimmune disease pathogenesis. The modified T cells are expanded under controlled conditions and administered as a single intravenous infusion after lymphodepleting conditioning. This dual-target CAR-T approach is intended to provide broad and sustained depletion of pathogenic B-cell populations and to promote immune system rebalancing in patients with relapsed or refractory autoimmune diseases.

Autologous CD19-BCMA Dual-Target CAR T-Cell Therapy (Fixed Dose)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years (inclusive), of any sex.
• Patients with failure of prior single-target CD19 or BCMA therapy, with a washout period of at least 6 months since the last treatment.
• Disease-specific criteria for different indications:
• Relapsed/Refractory Moderate-to-Severe Systemic Lupus Erythematosus (SLE)
• Participants must meet all of the following:
• Diagnosis of SLE according to the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus.
• At screening, positive antinuclear antibody (ANA) (titer ≥1:80), and/or positive anti-dsDNA antibody, and/or positive anti-Sm antibody.
• Moderate-to-severe disease activity defined as: SLEDAI-2000 score ≥8 at screening; if hypocomplementemia and/or anti-dsDNA antibody contribute to the score, the clinical SLEDAI-2000 score (excluding low complement and/or anti-dsDNA) must be ≥6.
• A documented history of at least 6 months of stable standard-of-care therapy for SLE prior to screening, with active disease for at least 2 months before screening. Standard therapy includes stable use (alone or in combination) of one or more of the following: glucocorticoids (≤20 mg/day prednisone or equivalent), antimalarial drugs (hydroxychloroquine ≤400 mg/day; chloroquine ≤500 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs), biologic agents (rituximab, belimumab, telitacicept), and other immunosuppressive or immunomodulatory agents including mycophenolate mofetil (≤2 g/day), azathioprine (≤2 mg/kg/day), methotrexate (≤20 mg/week), etc.
• Relapsed/Refractory Systemic Sclerosis (SSc)
• Participants must meet all of the following:
• Diagnosis of SSc according to the 2013 EULAR/ACR Classification Criteria for Systemic Sclerosis.
• Diffuse cutaneous SSc as defined by LeRoy et al. (1988), characterized by extensive skin fibrosis involving areas proximal to the elbows and/or knees.
• Presence of interstitial lung disease (ILD) at screening, with forced vital capacity (FVC) 45-70% predicted, or diffusing capacity for carbon monoxide (DLCO) 40-70% predicted.
• Relapsed/refractory disease defined as inadequate response to prior standard therapy or relapse after remission. Standard therapy includes glucocorticoids, cyclophosphamide, and at least one immunosuppressive or immunomodulatory agent administered for ≥6 months (e.g., azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, telitacicept).

You may not qualify if:

• \. Prior history of, or concurrent, other active malignancies, including malignancy-associated polymyositis/dermatomyositis. Exceptions include cervical carcinoma in situ, noninvasive basal cell or squamous cell skin cancer, localized prostate cancer treated with curative intent, or ductal carcinoma in situ after curative surgery, provided the participant is considered cured or has been disease-free for at least 2 years.
• Severe pulmonary disease within the past 3 months, such as moderate-to-severe pulmonary arterial hypertension (mean pulmonary artery pressure \>60 mmHg by echocardiography), requirement for supplemental oxygen via reservoir mask at screening, or requirement for noninvasive or invasive mechanical ventilation.
• At screening, serum IgA, IgG, and IgM below the lower limit of normal (LLN). 4.Use of any of the following medications or therapies within the specified time windows:
• Use of B-cell-depleting therapy within 1 month prior to screening and assessed by the investigator as not having failed therapy, including agents targeting CD19, CD20, CD22, CD52, CD38, or BCMA (monoclonal antibodies or bispecific antibodies).
• High-dose intravenous human immunoglobulin (IVIG) within 1 month prior to screening.
• Therapeutic-dose systemic corticosteroids within 24 hours prior to lymphodepleting conditioning (prednisone \>20 mg/day or equivalent).
• Corticosteroid pulse therapy within 2 weeks (defined as prednisone ≥500 mg/day or equivalent).
• Telitacicept within 2 weeks prior to screening, or belimumab within 3 weeks prior to screening.
• \. History of severe central nervous system (CNS) disease or related symptoms within the past 6 months (simple trigeminal neuralgia excluded), including but not limited to neuropsychiatric lupus, cerebrovascular disease, encephalitis, brain injury, aneurysm, cerebellar disease, organic brain syndrome, Parkinson's disease, as well as symptoms such as seizures/convulsions, aphasia, or dementia.
• \. Lupus crisis within 3 months prior to screening, such as active CNS lupus, severe autoimmune hemolytic anemia, severe immune thrombocytopenic purpura, severe granulocytopenia, severe myocardial injury, severe lupus pneumonitis or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis, or other severe lupus manifestations.
• \. Severe renal disease, including severe lupus nephritis within 8 weeks prior to screening (defined as urine protein \>4 g/24 hours, or serum creatinine \>1.5 × ULN, or creatinine clearance \<30 mL/min by Cockcroft-Gault), active nephritis requiring use of protocol-prohibited medications, or nephritis requiring prednisone \>500 mg/day (or equivalent systemic corticosteroids) for ≥14 days.
• Severe hypersensitivity/allergy to any lymphodepleting conditioning agent used in this study or to any component related to CAR T-cell manufacture/culture.
• Hepatitis B: positive HBsAg with detectable HBV DNA in peripheral blood;Hepatitis C: positive anti-HCV with detectable HCV RNA; Syphilis: RPR/TRUST titer ≥1:8; HIV: positive HIV antibody.
• Uncontrolled fungal, bacterial, or viral infection, or any other infection that, in the investigator's judgment, makes the participant unsuitable for study participation.
• \. History of major organ transplantation (e.g., heart or lung transplantation).

Sponsors & Collaborators

• Beijing Boren Hospital: lead

Study Sites (1)

Beijing GoBroad Boren Hospital

Beijing, 100070, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Scleroderma, Systemic; Myositis; Sjogren's Syndrome; Anemia, Hemolytic, Autoimmune; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous 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; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases

Central Study Contacts

Yajing Zhang

CONTACT

+86 18501333856; yajing_cart66@126.com

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: January 4, 2026
• First Posted: January 22, 2026
• Study Start: November 6, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

CN (1)