A Clinical Study of Dual-Target, Universal CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus

A Phase I/IIa Clinical Study to Evaluate Universal Allogeneic CAR-T Cells (QT-019B) Targeting CD19 and BCMA for the Treatment of Refractory Systemic Lupus Erythematosus

This study is a single-arm, open-label clinical study designed to evaluate the safety and tolerability of QT-019B in subjects with refractory SLE and to determine the RD. The study has two phases: dose escalation and dose expansion, with a planned enrollment of 18-24 subjects.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: QT-019B Cell Injection

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhijiang Wang; Phone Number: +86 151 5712 6379; Email: zhijiang.wang@qihanbio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Mengtao Li, PhD; Phone Number: +86 10 6915 1188; Email: mengtao.li@cstar.org.cn
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of USTC Anhui Provincial Hospital
      • Contact: Zhu Chen, PhD; Phone Number: 0551-62283114; Email: doczchen@ustc.edu.cn
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Qiubai Li, PhD; Phone Number: 027-85726375; Email: qiubaili@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥18 years and ≤65 years at screening, gender is not limited.
• 2. Subjects diagnosed with systemic lupus erythematosus according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria.
• 3. Meets the criteria for refractory SLE: a) Must have received adequate standard treatment prior to screening, including glucocorticoids, immunosuppressants, biologics. b) Refractory SLE is defined as a failure to respond, or a documented adverse event or intolerance to glucocorticoids combined with other immunosuppressive therapies. The patient should have had received treatment with courses of at least two different non glucocorticoid immunosuppressive therapies (not necessarily simultaneously), at least one of which is a B cell-depleting biological agent such as belimumab, rituximab (unless such drugs are deemed contraindicated by the investigator or such drugs are not readily available to the patient).
• 4. Positive serological test during the screening period, for at least one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (above the ULN), or anti-Sm (above the ULN), or other disease related autoantibodies (abovethe ULN).
• 5. At screening: a) SLE with or without Lupus Nephritis with SLEDAI-2K≥6. b) Severe, refractory SLE-ITP which is characterized by platelet count < 30×109/L, or < 50×109/L accompanied by a bleeding tendency.
• 6. Important organ functions during the screening period must meet the following requirements (excluding abnormalities related to SLE): a) Bone marrow function must meet the following: a. Neutrophil count ≥0.5×109/L; b. Hemoglobin ≥ 60g/L. b) Liver function: Alanine aminotransferase (ALT) ≤ 2×ULN, Aspartate aminotransferase (AST) ≤ 2×ULN, Total bilirubin (TBil) ≤ 2×ULN. c) Renal function: Creatinine clearance (CrCl) ≥ 30 ml/min (Cockcroft/Gault formula).
• 7. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must use medically approved contraceptive measures or abstain from sex during the study treatment period and for at least 12 months after the end of the study treatment; female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to study enrollment and must not be breastfeeding.
• 8. Voluntarily participate in this clinical study, sign the informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

• 1. Presence or definite history of central nervous system disorders, such as seizures, epilepsy, cerebrovascular accident (ischemic/hemorrhagic), cerebral edema, paralysis, aphasia, severe brain injury, dementia, Parkinson's disease, cerebellar disease, encephalitis, central nervous system vasculitis, or mental illness. If epilepsy caused by lupus is stable without seizures for 1 year before screening, screening may be performed.
• 2. Need for hemodialysis or high-dose corticosteroid therapy (prednisone ≥1.5 mg/kg/day or equivalent corticosteroid therapy ≥14 days) within 2 months before screening.
• 3. A large amount of serous cavity effusion with compressive symptoms that cannot be controlled after treatment (such as pleural effusion, ascites).
• 4. In the two years prior to the screening, subjects with other active autoimmune diseases (such as Crohn's disease or rheumatoid arthritis), except for SLE and its related conditions (such as SLE-induced thrombocytopenic purpura or SLE-associated autoimmune hemolytic anemia), as well as autoimmune thyroid disease and secondary Sjögren's disease.
• 5. Hematopoietic dysfunction that does not fulfill the criteria for SLE and its related ITP as determined by a bone marrow aspirate and/or biopsy, or subjects who have received or are waiting for hematopoietic stem cell/bone marrow transplantation or organ transplantation.
• 6. Subjects who have previously received gene-modified cell therapy, such as TCR-T, CAR-T, CAR-NK cells, and others.
• 7. Subjects who have used any other investigational drug for SLE within 4 weeks prior to screening.
• 8. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer above the upper limit of detection, subjects with positive hepatitis C virus (HCV) antibody and positive peripheral blood HCV RNA, subjects with positive human immunodeficiency virus (HIV) antibody, subjects with positive syphilis test.
• 9. Uncontrolled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg) within one month prior to screening, or any other serious cardiovascular diseases that could present potentially significant risks for participation in the study. Any of the following cardiovascular disease history within 6 months prior to screening: QTc prolongation syndrome or QTc interval >480 ms, complete left bundle branch block, second/third degree atrioventricular block, severe uncontrolled arrhythmia requiring medication, history of chronic congestive heart failure within 6 months prior to screening, NYHA≥3, cardiac ejection fraction <45%, myocardial infarction, cardiac angioplasty or stent implantation, unstable angina, severe pericardial disease, or other clinically significant heart disease within 6 months prior to screening.
• 10. A documented history of symptomatic deep vein thrombosis or pulmonary embolism within six months prior to the screening, or the presence of clinically significant pleural effusion, or an oxygen saturation level below 92% while breathing ambient air.
• 11. History of treated or untreated malignancy of any organ system within 5 years prior to screening (excluding basal cell carcinoma of the skin, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, follicular or papillary thyroid cancer, and other tumors with good prognosis).
• 12. Participants with any active infection, and any infection requiring systemic antimicrobial therapy within the past 30 days.
• 13. Any additional factors that the investigator thinks could put the subjects at risk, affect their adherence to treatment, disrupt the study's execution, or influence the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: QT-019B Cell Injection; The study will begin by enrolling the first subject in Dose A (1×106/kg), followed by a 14-day interval before enrolling the following subjects at this dose level. Upon completing the DLT observation period for Dose Group A: 1) if no DLTs are observed, the SRC may choose to proceed to Dose Group B (3×106/kg). 2) if one DLT is noted, the SRC may opt to add 3 more subjects to Dose A, and if a second DLT occurs, the SRC may consider ending the study or reducing the dose. 3) if two DLTs are observed at Dose A, the SRC may decide to terminate the study or reduce the dose.

Drug: QT-019B Cell Injection; The study will begin by enrolling the first subject in Dose A (1×106/kg), followed by a 14-day interval before enrolling the following subjects at this dose level. Upon completing the DLT observation period for Dose Group A: 1) if no DLTs are observed, the SRC may choose to proceed to Dose Group B (3×106/kg). 2) if one DLT is noted, the SRC may opt to add 3 more subjects to Dose A, and if a second DLT occurs, the SRC may consider ending the study or reducing the dose. 3) if two DLTs are observed at Dose A, the SRC may decide to terminate the study or reduce the dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Dose-Limiting Toxicities (DLTs)	A Dose-Limiting Toxicity (DLT) is defined as a specific set of severe (Grade 3 or higher) treatment-related toxicities (including hematological and non-hematological toxicities) that occur during the DLT observation period. DLTs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. This measure is used to determine the Recommended Dose (RD).	Within 28 days following QT-019B administration.
Number of Subjects with Adverse Events (AEs)	This includes the frequency and severity of Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs). Severity will be assessed using NCI-CTCAE v5.0. This includes systemic toxicities and cell-therapy-specific events such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).	From QT-019B administration through Day 28 (Acute Safety Period).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) Score.	The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) is a validated clinical instrument used to assess disease activity in SLE. The scale ranges from a minimum score of 0 to a maximum score of 105. Higher scores indicate a worse outcome (greater disease activity).	Day 28, 60, 90, 180, 270, 360, 450, 540, 630, and 730.
Change from Baseline in Physician's Global Assessment (PGA) Score	The Physician Global Assessment (PGA) is a visual analog scale used by the investigator to rate the patient's overall disease activity. The scale ranges from a minimum of 0 (no disease activity) to a maximum of 3 (severe disease activity). Higher scores indicate a worse outcome.	Day 28, 60, 90, 180, 270, 360, 450, 540, 630, and 730.
Change from Baseline in British Isles Lupus Assessment Group 2004 (BILAG-2004) Index.	The British Isles Lupus Assessment Group 2004 (BILAG-2004) index measures disease activity across 9 organ systems. For the purpose of numerical analysis, category scores (A-E) are often converted to a total numerical score. The scale ranges from a minimum of 0 to a maximum of 72. Higher scores indicate a worse outcome (higher disease activity).	Day 28, 60, 90, 180, 270, 360, 450, 540, 630, and 730
Peak Concentration (Cmax) of QT-019B in Peripheral Blood	The maximum observed concentration of QT-019B (CAR-transgene copies) in peripheral blood measured via qPCR/ddPCR after administration. This represents the peak expansion of the cell product.	From Day 0 through Day 28 post-administration.
Area Under the Concentration-Time Curve (AUC 0-28d) of QT-019B	The total systemic exposure of QT-019B in peripheral blood over the first 28 days post-infusion, calculated using the linear trapezoidal rule.	From Day 0 through Day 28 post-administration.
Time to Reach Peak Concentration (Tmax) of QT-019B	The time (in days) from the start of QT-019B infusion to the observation of the maximum concentration (Cmax) in peripheral blood.	From Day 0 through Day 28 post-administration.

Collaborators and Investigators

• Sponsor: Hangzhou Qihan Biotech Co., Ltd.
• Investigators: Principal Investigator: Mengtao Li, PhD, Peking Union Medical College Hospital; Principal Investigator: Zhu Chen, PhD, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); Principal Investigator: Qiubai Li, PhD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Principal Investigator: Ting Zhang, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Refractory Systemic Lupus Erythematosus; Universal Allogeneic CAR-T Cells
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: QT-019B-001CN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No