Allogeneic CD19/BCMA CAR-T for B Cell-Related Autoimmune Disease

NCT07507201 | Recruiting Early Phase 1

• 1 other identifier: QH-ZE-03
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory, open-label, single-arm Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219C. QT-219C is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219C .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .

Conditions

Autoimmune Diseases; Systemic Lupus Erthematosus (SLE); Multi-Drug Resistant Nephrotic Syndrome; IgA Nephropathy (IgAN); Systemic Sclerosis (SSc); ANCA Associated Systemic Vasculitis

Keywords

UCART; Multi-Drug Resistant Nephrotic Syndrome; Systemic Lupus Erthematosus; IgAN - IgA Nephropathy; Systemic Sclerosis (SSc); ANCA-Associated Vasculitis (AAV)

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose-Limiting Toxicities (DLTs)

  The number, frequency, and severity of DLTs experienced by subjects after the first infusion of QT-219C. DLTs are defined by NCI-CTCAE 5.0 and ASTCT consensus for CRS and neurotoxicity.

  Day 0 to Day 28 post-infusion.

• Incidence of Adverse Events (AEs)

  Evaluation of the number, frequency, and severity of all adverse events, including Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs).

  Up to Day 90 post-infusion.

• Preliminary Clinical Efficacy at Day 90

  Assessment of disease-specific clinical response rates : * SLE: Proportion of subjects achieving SRI-4, LLDAS, or DORIS criteria. * Nephrotic Syndrome/IgA Nephropathy: Proportion of subjects achieving Complete Remission (CR) or Partial Remission (PR)/Proteinuria Remission. * Systemic Sclerosis: Changes in CRISS scores. * ANCA-associated Vasculitis: Proportion of subjects achieving CR or PR.

  Day 90 post-infusion.

Secondary Outcomes (6)

• Cmax of CAR-T cells [PK parameter]

  Within 28 Days After UCAR T-cell Infusion

• Tmax of CAR-T cells [PK parameter]

  Within 28 Days After UCAR T-cell Infusion

• AUC 0-28d of UCAR-T cells [PK parameter]

  Within 28 Days After UCAR T-cell Infusion

• The degree of B cell depletion [PD parameter]

  Up to 12 Months After UCAR T-cell Infusion

• The concentration levels of IL-6 [PD parameter]

  Up to 12 Months After UCAR T-cell Infusion

Other Outcomes (3)

• Growth and Development Assessment

  Until the subject reaches 18 years of age.

• Growth and Development Assessment

  Until the subject reaches 18 years of age.

• Growth and Development Assessment

  Until the subject reaches 18 years of age.

Study Arms (1)

UCAR T-cell group

EXPERIMENTAL

This is a single-arm, open-label study where subjects with B-cell related autoimmune diseases will undergo lymphodepletion followed by a single intravenous infusion of QT-219C cells. The study includes a dose-escalation phase using a "3+3" design followed by a dose-expansion phase.

Biological: UCAR T-cell

Interventions

UCAR T-cell BIOLOGICAL

A universal allogeneic CAR-T cell product targeting both CD19 and BCMA

UCAR T-cell group

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Major organ function must meet the following criteria (exceptions allowed for abnormalities related to autoimmune disease activity):
• )Bone Marrow Function: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; b. Hemoglobin ≥ 60 g/L; c. Platelet count ≥ 30 × 10⁹/L.
• )Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
• )Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR \< 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
• )Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
• )Pulmonary Function: No severe pulmonary disease, and SpO₂ ≥ 92%.
• Women of childbearing potential must use medically acceptable contraception or practice abstinence during the study treatment period and for at least 12 months after the end of study treatment.
• Informed consent: The participant (and guardian if the participant is a minor) must provide written informed consent, indicating understanding of the study purpose and procedures and willingness to participate.
• SLE:
• Age ≥ 5 years.
• Meets the 2012 SLICC or 2019 EULAR/ACR classification criteria for SLE.
• Must meet at least one of the following adequate treatment conditions:
• )Active disease persists despite adequate treatment with glucocorticoids (≥1 mg/kg/day prednisone or equivalent dose of other corticosteroids) in combination with at least two immunosuppressants or biologic agents for at least 3 months, or affected organ function has failed to improve; or inability to taper glucocorticoid dosage to ≤5 mg/day after 6 months of conventional treatment;
• )Patients who have developed intolerable drug toxicity during conventional therapy, or have contraindications precluding standard treatment, or have experienced multiple treatment failures-may be considered for enrollment following full informed consent by the investigator and the patient or legal guardian;
• )SLEDAI-2K Criteria: SLEDAI-2K score ≥8; or SLEDAI-2K score ≥6 combined with at least one BILAG-2004 Category A or two Category B organ system involvements (or both).

You may not qualify if:

• \. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, tocilizumab), or subjects with a history of severe allergic reactions.
• Subjects with grade III or IV heart failure (NYHA classification).
• Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs.
• \. Uncontrollable infection, or active infection that requires systemic treatment at screening.
• \. Had active pulmonary tuberculosis at screening.
• \. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive.
• \. History of severe herpes infection prior to screening, such as herpetic encephalitis, ocular herpes, or disseminated herpes; Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening.
• \. Patients had active central nervous system disease.
• \. Patients with malignant diseases such as tumors before screening.
• \. Secondary or congenital immunodeficiency.
• \. History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of QT-019B, except for lupus.
• \. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening.
• \. Received live vaccine within 4 weeks before screening.
• \. Tested positive in Blood pregnancy test.
• \. Patients who had participated in other clinical trials and received any intervention within 3 months before enrollment.

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases; Nephrotic Syndrome; Glomerulonephritis, IGA; Scleroderma, Systemic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Condition Hierarchy (Ancestors)

Immune System Diseases; Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Central Study Contacts

J Mao, PhD

CONTACT

13516819071; maojh88@zju.edu.cn

Qiuyu Li, MD

CONTACT

17794588355; liqiuyu1992@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: April 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)