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IgG4 Related DiseasePhase 2BC19IGG4NCT07148791

Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease

A Phase 2 study testing Anti-BCMA-CD19 CAR-T cells in people with IgG4 Related Disease and B-cell Mediated Autoimmune Disorders, run by Chinese PLA General Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The goal of this clinical trial is to test the safety and potential benefit of a new immune cell therapy called anti-BCMA-CD19 CAR-T cells in adults (18-75 years) with IgG4-related disease (IgG4-RD) that has come back or not improved after standard treatments such as glucocorticoids or rituximab. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Anti-BCMA-CD19 CAR-T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteChina
Study dates
5 Sep 2025to 31 Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To participate, subjects must meet all of the following criteria:
  • Aged 18 to 75 years, inclusive, regardless of sex.
  • Meet the 2019 ACR/EULAR classification criteria for IgG4-related disease.
  • Involvement of two or more important systems/sites (including but not limited to the pancreas, bile ducts, kidneys and dura mater).
  • Relapsed or refractory IgG4-RD: The disease either remains active after 3 months of glucocorticoid and/or rituximab therapy or relapses within 6 months post-treatment.
  • Important organ function meeting the following conditions:
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  • Bone marrow: (i) neutrophil count ≥1×10^9/L (excluding disease-related neutropenia); (ii) hemoglobin ≥60 g/L.
  • Hepatic function: ALT≤3×ULN (elevation caused by disease may be excluded); AST≤3×ULN (elevation caused by disease may be excluded); TBIL≤1.5×ULN (elevation caused by disease may be excluded).
  • Renal function: creatinine clearance (Cockcroft-Gault formula) ≥30 ml/min (excluding acute decline due to disease).
  • Coagulation: international normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN
  • Cardiac function: stable hemodynamics.
  • Women of childbearing potential and male subjects with partners of childbearing potential must use medically accepted contraception or abstain during study treatment and for at least 12 months after the end of treatment. Women of childbearing potential must have a negative serum HCG test within 7 days before enrollment and must not be breastfeeding.
  • Voluntary participation in this clinical study with signed informed consent and willingness to comply with study procedures and follow-up.
  • Patent superficial peripheral veins adequate for intravenous infusion.

Who cannot join

  • Subjects will be excluded if any of the following criteria are met:
  • History of severe drug allergy or allergic constitution.
  • Current or suspected uncontrollable or treatment-requiring fungal, bacterial, viral or other infections.
  • Central nervous system disease (excluding disease-related epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis).
  • Cardiac insufficiency that precludes participation.
  • Congenital immunoglobulin deficiency.
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  • Congenital malformation or nutritional disorder causing severe organ impairment.
  • History of malignancy within the past five years.
  • End-stage renal failure.
  • Positive hepatitis B surface antigen and hepatitis B core antibody with HBV-DNA titers above the assay limit of detection; positive hepatitis C antibody with HCV-RNA positivity; positive human immunodeficiency virus antibody; positive syphilis serology.
  • Psychiatric disorders or severe cognitive impairment.
  • Participation in other clinical trials within three months before enrollment.
  • Receipt of any investigational drug within 12 weeks before screening or within five half-lives of the agent (whichever is longer).
  • Pregnant or intending to become pregnant.
  • Any other reason deemed by the investigator to preclude enrollment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

YIWEN WANG, M.D. contact

+86 010-55499314

yiwenvera@163.com

YUFEI GUO, M.M. contact

+86 010-55499314

dt_guoyf0412@outlook.com

China1 site, 1 recruiting

  • Department of Rheumatology and Immunology, the First Medical Center, Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100853

    YUFEI GUO, M.M., +86 010-55499314, dt_guoyf0412@outlook.com

    JIAN ZHU, M.D./Ph.D.

    Recruiting

Other trials in China

About this study

Official title: Exploratory Clinical Study of Anti-BCMA-CD19 CAR-T Cell Therapy for Relapsed/Refractory IgG4-Related Disease

The goal of this clinical trial is to test the safety and potential benefit of a new immune cell therapy called anti-BCMA-CD19 CAR-T cells in adults (18-75 years) with IgG4-related disease (IgG4-RD) that has come back or not improved after standard treatments such as glucocorticoids or rituximab.

The main questions this study aims to answer are:

Read more
  • What medical problems (side effects) occur after receiving anti-BCMA-CD19 CAR-T cell therapy?
  • Does anti-BCMA-CD19 CAR-T cell therapy improve IgG4-RD disease activity scores at 12 weeks and 26 weeks?

Participants will:

  • Have their own blood immune cells collected by a procedure called leukapheresis
  • Receive short-term chemotherapy to prepare the immune system
  • Receive one intravenous infusion of anti-BCMA-CD19 CAR-T cells
  • Return for regular clinic visits over 26 weeks for safety checks, blood tests, and imaging
  • May be followed for up to one year in total
Read the detailed description

This is a Phase 2, open-label, single-arm exploratory clinical trial using a 3+3 dose-escalation design to assess the safety, feasibility, and preliminary efficacy of autologous anti-BCMA-CD19 chimeric antigen receptor T (CAR-T) cell therapy in patients with relapsed or refractory IgG4-related disease (IgG4-RD).

Background IgG4-RD is a chronic, immune-mediated fibroinflammatory disorder that can involve multiple organs, including the pancreas, bile ducts, salivary glands, kidneys, lungs, and retroperitoneum. Although standard treatments such as glucocorticoids and anti-CD20 monoclonal antibodies (e.g., rituximab) are effective for most patients, some develop treatment resistance, frequent relapses, or contraindications to conventional immunosuppressive agents. This creates an unmet clinical need for novel therapeutic strategies.

Recent translational studies show that IgG4-RD lesions often contain abundant CD19+ B cells, plasmablasts, and long-lived plasma cells expressing B-cell maturation antigen (BCMA), many of which may be resistant to conventional B-cell depletion. Dual-target CAR-T cells directed against both CD19 and BCMA may achieve more complete depletion of pathogenic B-lineage cells and offer a promising treatment for refractory IgG4-RD.

Methods Eligible participants will undergo leukapheresis for autologous peripheral blood mononuclear cell (PBMC) collection. Cells will be transduced ex vivo with a lentiviral vector encoding a CAR construct targeting CD19 and BCMA, then expanded and prepared for infusion. Lymphodepletion chemotherapy with cyclophosphamide (250 mg/m^2/day, IV) and fludarabine (30 mg/m^2/day, IV) will be given on Days -5 to -3. The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's condition.

CAR-T cells will be infused on Day 0 at one of three sequential dose levels (1×10^6, 2×10^6, or 3×10^6 CAR+ T cells/kg, ±20%). Participants will be followed regularly for safety (adverse events [AEs], serious adverse events [SAEs], cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS]), pharmacokinetics (CAR-T cell expansion and persistence), and immunologic responses.

Endpoints The primary endpoints are safety (incidence of dose-limiting toxicities [DLTs] within 28 days post-infusion) and efficacy (change in IgG4-RD Responder Index [RI] at Week 12 and Week 26). Secondary endpoints include changes in target lesion size, serum IgG4, IgE, and eosinophil counts, as well as histopathologic changes in affected tissue.

Exploratory Analyses Exploratory studies will assess immune cell profiles in blood, bone marrow, and tissue biopsies using flow cytometry, multiplex cytokine assays, and spatial or single-cell transcriptomic techniques.

Being tested
Anti-BCMA-CD19 CAR-T cells
Keywords
IgG4 related disease, CAR-T therapy, BCMA/CD19 CAR-T
Medical subject headings
Immunoglobulin G4-Related Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-BCMA-CD19 CAR-T cellsBiological

    Also called BC19, CD19/BCMA dual-target CAR-T cell therapy

    Anti-BCMA-CD19 CAR-T cell injection is an autologous, dual-target chimeric antigen receptor T-cell therapy designed to target CD19 and BCMA antigens. Peripheral blood mononuclear cells (PBMCs) are collected from each participant and modified ex vivo using lentiviral transduction to express the CAR construct. Lymphodepletion with cyclophosphamide (250 mg/m^2/day, IV) and fludarabine (30 mg/m^2/day, IV) is administered for 3 days (Day -5 to Day -3). The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's clinical condition. CAR-T cells are infused intravenously on Day 0 at one of three dose levels (1x10^6, 2x10^6, or 3x10^6 CAR+ T cells/kg, ±20%). This product is being investigated in patients with relapsed or refractory IgG4-related disease (IgG4-RD) to assess safety and preliminary efficacy.

Study groups in NCT07148791
Study groupRoleWhat they receive
Anti-BCMA-CD19 CAR-T cellsExperimentalParticipants will undergo leukapheresis for autologous T-cell collection, followed by ex vivo transduction with a lentiviral vector encoding a dual-target CAR against BCMA and CD19. After lymphodepletion chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (250 mg/m²/day) for 3 consecutive days, participants will receive a single intravenous infusion of the manufactured CAR-T cells at the assigned dose level. Post-infusion, participants will be monitored for safety, tolerability, and preliminary efficacy through Week 52.
Receives: Biological: Anti-BCMA-CD19 CAR-T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety - Incidence of Dose-Limiting Toxicity (DLT) and Adverse Events Related to CAR-T Cells

    Any grade ≥3 toxicity related to CAR-T cells within 28 days post-infusion is considered a DLT, except:

    • Grade 3 CRS resolving to ≤ grade 2 within 3 days;
    • Grade 3/4 TLS <7 days;
    • Hematologic: grade 3 neutropenia/anemia/thrombocytopenia at any time or grade 4 <14 days (<21 days for thrombocytopenia); other cytopenias excluded;
    • Non-hematologic: fever (incl. febrile neutropenia), grade 3 diarrhea <7 days, grade 3 nausea/vomiting <7 days, grade 3 fatigue <7 days;
    • Grade 3/4 elevations in liver enzymes, bilirubin, creatinine, or BUN <7 days;
    • Asymptomatic lipase elevation without pancreatitis;
    • Asymptomatic grade 3 non-hematologic lab abnormality reversible <7 days (to baseline or ≤ grade 2).

    Safety monitoring includes AEs, SAEs, AESIs, CRS, and ICANS, with grading and frequency recorded.

    Measured: Baseline to Week 26

  2. Efficacy - Changes in IgG4-RD RI

    IgG4-RD Responder Index is a validated score used to assess disease activity

    Measured: Baseline, Week 12 and Week 26

Secondary outcomes (13)

  1. PK: Cmax of CAR-T Cells

    Peak CAR transgene copies in peripheral blood

    Measured: Baseline to Week 26

  2. PK: Tmax of CAR-T Cells

    Time to peak CAR transgene level

    Measured: Baseline to Week 26

  3. PK: AUC0-28d of CAR-T Cells

    Area under the curve of CAR transgene copies over 28 days

    Measured: Baseline, Week 4

  4. PK: AUC0-90d of CAR-T Cells

    Area under the curve of CAR transgene copies over 90 days

    Measured: Baseline, W12

  5. PK: Persistence (Tlast) of CAR-T Cells

    Last measurable CAR transgene level

    Measured: Baseline to Week 26

  6. PD: CD19+ B-cell Count

    Flow cytometric quantification of circulating CD19⁺ B cells

    Measured: Baseline to Week 26

  7. PD: CAR-T Gene Expression

    Changes in CAR-T cell-associated gene expression

    Measured: Baseline to Week 26

  8. Lesion Size on Imaging

    Radiographic measurement of involved lesion(s)

    Measured: Baseline, Week 12 and Week 26

  9. Serum IgG4

    Serum IgG4 concentration (mg/dL)

    Measured: Baseline, Week 12 and Week 26

  10. Serum IgE

    Serum IgE concentration (IU/mL)

    Measured: Baseline, Week 12 and Week 26

  11. Total IgG

    Total IgG concentration (mg/dL)

    Measured: Baseline, Week 12 and Week 26

  12. Absolute Eosinophil Count

    Eosinophil count in peripheral blood (cells/µL)

    Measured: Baseline, Week 12 and Week 26

  13. Histopathology of Lesion

    Semi-quantitative scoring of inflammation, fibrosis, and IgG4⁺ plasma cell infiltration

    Measured: Baseline, Week 26 or time of B-cell recovery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2025
  2. Study start5 Sep 2025 (estimated)
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is an open-label, single-arm, exploratory interventional study using a 3+3 dose-escalation design. Adults with relapsed or refractory IgG4-related disease will receive autologous anti-BCMA-CD19 CAR-T cells. The study includes a lymphodepletion phase, a cell infusion phase, and serial efficacy and safety assessments through Week 26. Three dose levels (1x10\^6, 2x10\^6, and 3x10\^6 CAR+ T cells/kg) will be evaluated sequentially. No control group is included.
Masking
None (open label)
Enrolment
9 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07148791
Sponsor's protocol ID
BC19IGG4
Acronym
BC19IGG4
Status last verified
Sep 2025
First submitted
30 Jul 2025
Last updated
3 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Access to the data underlying this study can be obtained from the corresponding author upon reasonable request and subject to any required ethical approvals.

Publications

  • Sun Y, Huang S, Zhang B, Peng Y, Lu H, Jia Y, Sun R, Zhang F, Zhou J, Peng L, Li M, Zhang W, Fei Y. Efficacy and safety of anti-CD19 CAR-T in a mouse model of IgG4-related disease. Int Immunopharmacol. 2025 Jan 3;145:113779. doi: 10.1016/j.intimp.2024.113779. Epub 2024 Dec 12.

    PubMed 39672025

  • Zhang Y, Liu D, Zhang Z, Huang X, Cao J, Wang G, Du X, Wang Z, Yang M, Luo T, Liu S, Zhang W, Sheng Y, Li H, Zhang W, Chen H, Zhang S, Wang X, Meng W, Zong S, Shi M, Zheng J, Cui G. Bispecific BCMA/CD19 targeted CAR-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: a case report. J Neurol. 2024 Jul;271(7):4655-4659. doi: 10.1007/s00415-024-12367-4. Epub 2024 Apr 11. No abstract available.

    PubMed 38602546

  • Shi M, Wang J, Huang H, Liu D, Cheng H, Wang X, Chen W, Yan Z, Sang W, Qi K, Li D, Zhu F, Li Z, Qiao J, Wu Q, Zeng L, Fei X, Gu W, Miao Y, Xu K, Zheng J, Cao J. Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial. Nat Commun. 2024 Apr 20;15(1):3371. doi: 10.1038/s41467-024-47801-8.

    PubMed 38643278

  • Wang Y, Cao J, Gu W, Shi M, Lan J, Yan Z, Jin L, Xia J, Ma S, Liu Y, Li H, Pan B, Chen W, Fei X, Wang C, Xie X, Yu L, Wang G, Li H, Jing G, Cheng H, Zhu F, Sun H, Sang W, Li D, Li Z, Zheng J, Xu K. Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. J Clin Oncol. 2022 Jul 10;40(20):2246-2256. doi: 10.1200/JCO.21.01676. Epub 2022 Mar 25.

    PubMed 35333600

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-BCMA-CD19 CAR-T cells in people with IgG4 Related Disease and B-cell Mediated Autoimmune Disorders, run by Chinese PLA General Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact YIWEN WANG, M.D. (+86 010-55499314, yiwenvera@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety - Incidence of Dose-Limiting Toxicity (DLT) and Adverse Events Related to CAR-T Cells (time frame: Baseline to Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07148791, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.

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