NCT07507201

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

An Exploratory Clinical Study Evaluate the Safety and Efficacy of Universal Universal Allogeneic CAR-T Cells Targeting CD19 and BCMA in the Treatment of B Cell-Related Autoimmune Disease

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine · Academic / Other
• Sex: All
• Age: 3 Years
• Healthy volunteers: Not accepted

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 .

Detailed description

* 1\. Background and Rationale * This study investigates a novel cell therapy for patients with relapsed or refractory B-cell-mediated autoimmune diseases (AID). QT-219C Cell Injection is a universal allogeneic CAR-T cell product derived from healthy donors, designed to target both CD19 and BCMA. * Dual-Targeting Design: By targeting both CD19+ B cells and BCMA+ plasma cells, the therapy aims to achieve deep and extensive depletion of pathogenic immune cells, potentially leading to immune "resetting". * Advanced Gene Editing: * Safety: The TRAC gene is knocked out to eliminate T-cell receptor (TCR) expression, thereby minimizing the risk of Graft-versus-Host Disease (GvHD). Immune Evasion: Genes including CIITA, HLA-A, HLA-B, and HLA-C are knocked out, while HLA-E is retained and a novel hypo-Y element is knocked in to reduce immunogenicity and resist rejection by host T and NK cells. * Enhanced Potency: The gene-X element is integrated to improve the expansion and persistence of the cells within the patient's body, even under conditions of reduced or no lymphodepletion. * 2\. Study Objectives * Primary Objective: To evaluate the safety, tolerability, and preliminary efficacy of QT-219C in subjects with B-cell-related autoimmune diseases, and to determine the Dose-Limiting Toxicities (DLTs). * Secondary Objective: To characterize the pharmacokinetics (PK, e.g., transgene copy numbers) and pharmacodynamics (PD, e.g., cytokine levels and B-cell depletion) of QT-219C. * Exploratory Objective: To explore correlations between baseline status (e.g., NK cell phenotype), PK/PD, safety, and efficacy, as well as the impact on growth and development (Tanner stage) in pediatric subjects. * 3\. Study Design and Dose Escalation This is an open-label, single-arm, dose-escalation, and expansion study. Dose Escalation: A standard "3+3" design is employed, with an estimated 6-15 subjects in this phase. * Enrollment Priority: Enrollment will prioritize older pediatric subjects. * 4\. Clinical Procedures * Screening (Day -28 to -5): Subjects provide informed consent and undergo baseline laboratory and imaging assessments. * Conditioning (Day -5 to -3): Subjects receive a lymphodepletion regimen. * Infusion (Day 0): Upon confirming adequate organ function and absence of active infection, a single intravenous dose of QT-219C is administered. * DLT Observation (Day 0 to 28): Subjects are closely monitored for 28 days post-infusion to assess hematologic and non-hematologic toxicities. * 5\. Follow-up and Efficacy Evaluation * Safety Management: Intensive monitoring for Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), GvHD, infections, and viral reactivation . * Efficacy Assessment: Evaluations are conducted at Days 28, 60, 90, and 180, with Day 90 and Day 180 serving as key clinical efficacy time points. * Long-term Follow-up: Starting six months post-infusion, subjects enter a long-term follow-up phase with visits every 3 months for up to 2 years or as clinically indicated.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	UCAR T-cell	A universal allogeneic CAR-T cell product targeting both CD19 and BCMA

Timeline

• Start date: 2026-04-01
• Primary completion: 2028-12-01
• Completion: 2029-12-01
• First posted: 2026-04-02
• Last updated: 2026-04-02

Locations

1 site across 1 country: China