Systemic Lupus Erythematosus (SLE)Phase 1NCT07439029
YTS109 in Pediatric Relapsed/Refractory Autoimmune Diseases
A Phase 1 study testing YTS109 cell in people with Systemic Lupus Erythematosus (SLE) and Diffuse Systemic Sclerosis, run by Children's Hospital of Fudan University at 1 site in China.
Trial summary
This exploratory, single-arm, open-label study will evaluate the safety and preliminary efficacy of YTS109 cell therapy in pediatric patients with relapsed/refractory autoimmune diseases, including systemic lupus erythematosus, diffuse systemic sclerosis, idiopathic inflammatory myopathies, and Sjögren's syndrome, as… Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Systemic Lupus Erythematosus (SLE), Diffuse Systemic Sclerosis, Idiopathic Inflammatory Myopathies (IIMs)
- What is being tested?
- YTS109 cell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- Mar 2026to Jul 2030
- Phase
- Phase 1
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 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- -
- Age 5 to <18 years at screening; sex not restricted.
- CD19 positivity: Presence of CD19-positive B cells in peripheral blood, confirmed by flow cytometry.
- Adequate major organ function, meeting all of the following criteria:
- 1）Bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (no colony-stimulating factor use within 2 weeks prior to testing; neutropenia attributable to the underlying disease may be allowed);
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- Hemoglobin ≥ 60 g/L. 2）Hepatic function: ALT ≤ 3 × ULN (exceptions allowed for elevations attributable to the underlying disease); AST ≤ 3 × ULN (exceptions allowed for elevations attributable to the underlying disease); Total bilirubin (TBIL) ≤ 1.5 × ULN (exceptions allowed for elevations attributable to the underlying disease).
- 3）Renal function: Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m², calculated using the Schwartz formula (exceptions allowed for reduced renal function attributable to the underlying disease).
- 4）Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and prothrombin time (PT) ≤ 1.5 × ULN.
- 5）Cardiac status: Hemodynamically stable. 4. Females of childbearing potential must be not pregnant and not breastfeeding during screening and throughout the study period.
- 5. The participant and the legal guardian are willing to participate, provide written informed consent, and can comply with study procedures and follow-up.
- Specific inclusion criteria:
- Recurrent refractory systemic lupus erythematosus
- 1. Meets the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE).
- 2. Active disease, defined as either: SELENA-SLEDAI ≥ 6 and at least one BILAG-2004 organ domain score of A (severe activity) or two domains scored B (moderate activity), or a combination thereof; or SELENA-SLEDAI ≥ 8.
- 3. Relapsed/refractory or intolerant to conventional therapy, defined as one of the following: Inadequate response after >3 months of conventional therapy; or intolerance to treatment-related adverse effects; or Disease flare/recurrence after achieving remission based on the LLDAS criteria. Conventional therapy is defined as treatment with glucocorticoids and cyclophosphamide, and one or more of the following immunomodulatory agents: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, or any biologic agent, including rituximab, belimumab, and telitacicept.
- 4. If renal involvement is present, a kidney biopsy must have been performed within 12 months prior to treatment, demonstrating active lesions or predominantly active lesions on pathology.
- Relapsing refractory/progressive diffuse systemic sclerosis
- Meets the 2013 ACR classification criteria for systemic sclerosis and is consistent with the diffuse cutaneous subtype (dcSSc).
- Positive for any antinuclear antibody (ANA) or systemic sclerosis-associated autoantibody.
- Evidence of diffuse cutaneous skin sclerosis and/or active interstitial lung disease (ILD), defined as ground-glass opacities on high-resolution computed tomography (HRCT).
- Inadequate response to conventional therapy for >3 months or disease relapse/recurrence after achieving remission. Conventional therapy is defined as treatment with glucocorticoids and cyclophosphamide, and one or more of the following immunomodulatory agents: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, JAK inhibitors, or any biologic agent, including rituximab, tocilizumab, TNF-α inhibitors (etanercept, adalimumab, infliximab), and telitacicept.
- Progressive disease, defined as either:
- 1） Rapid skin progression: mRSS increase >25%; or 2） Progressive lung disease: FVC decline ≥10%, or FVC decline ≥5% accompanied by DLCO decline ≥15%.
- Note: Criterion 4 or 5 must be met (either one is sufficient).
- Recurrent refractory/progressive inflammatory myopathy:
- 1. Meets the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies (including dermatomyositis [DM], polymyositis [PM], antisynthetase syndrome [ASS], and necrotizing myopathy [NM]).
- 2. Positive for myositis-specific and/or myositis-associated autoantibodies. 3. Evidence of active disease meeting either of the following:
- 1) Muscle involvement: CMAS < 30 and at least two abnormal findings among the following core measures: Physician Global Assessment (PhGA) ≥ 2, Patient/Parent Global Assessment (PtGA) ≥ 2, extra-muscular disease activity score ≥ 2, and/or serum muscle enzymes ≥ 1.5 × ULN; or 2) Interstitial lung disease (ILD): CMAS ≥ 30 but with active ILD, defined as ground-glass opacities on high-resolution computed tomography (HRCT).
- 4. Inadequate response to conventional therapy for >3 months, or intolerance to treatment-related adverse effects, or relapse/recurrence after achieving remission. Conventional therapy is defined as treatment with glucocorticoids and cyclophosphamide, and one or more of the following immunomodulatory agents: antimalarials, intravenous immunoglobulin (IVIG), azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, JAK inhibitors, or any biologic agent, including rituximab, tocilizumab, TNF-α inhibitors (etanercept, adalimumab, infliximab), and telitacicept.
- 5. Progressive disease, defined as worsening myositis or rapidly progressive interstitial lung disease (RP-ILD).
- Note: Criterion 4 or 5 must be met (either one is sufficient). Recurrent refractory sjogren's syndrome
- Meets the 2002 American-European Consensus Group (AECG) classification criteria for primary Sjögren's syndrome or the 2018 Japanese classification criteria.
- Active disease, defined as ESSDAI ≥ 6.
- Positive for anti-SSA/Ro antibodies.
- Inadequate response to conventional therapy for >3 months or relapse/recurrence after achieving remission. Conventional therapy is defined as treatment with glucocorticoids and cyclophosphamide, and one or more of the following immunomodulatory agents: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, or any biologic agent, including rituximab, belimumab, and telitacicept.
- Recurrent/refractory ANCA-associated vasculitis:
- Meets the 2022 ACR/EULAR classification criteria for ANCA-associated vasculitis, including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
- Positive for ANCA, defined as MPO-ANCA and/or PR3-ANCA positivity.
- Active vasculitis, defined as Paediatric Vasculitis Activity Score (PVAS) ≥ 15 (maximum score 65).
- Inadequate response to conventional therapy for >3 months or relapse/recurrence after achieving remission. Conventional therapy is defined as treatment with glucocorticoids and cyclophosphamide, and one or more of the following immunomodulatory agents: azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, or any biologic agent, including rituximab, belimumab, and telitacicept.
- Recurrent refractory/catastrophic antiphospholipid syndrome:
- 1. Meets the 2006 revised Sydney classification criteria for primary antiphospholipid syndrome (APS).
- 2. Positive for antiphospholipid antibodies (aPL) at medium to high titers, defined as lupus anticoagulant (LA), anti-β2-glycoprotein I (anti-β2GPI) IgG/IgM, and/or anticardiolipin (aCL) IgG/IgM, with ≥2 positive tests at least 12 weeks apart.
- 3. Relapsed/refractory APS, defined as recurrent thrombosis despite standard-of-care therapy, including:
- Anticoagulation with warfarin or another vitamin K antagonist (VKA) with INR maintained within the target therapeutic range, or therapeutic-dose low-molecular-weight heparin (LMWH), and
- Prior treatment with glucocorticoids and cyclophosphamide, with subsequent recurrent thrombosis.
- 4. Catastrophic antiphospholipid syndrome (CAPS), defined by fulfillment of all four criteria:1) Involvement of three or more organs, systems, and/or tissues; 2) Development of manifestations within one week; 3)Histopathologic confirmation of small-vessel thrombosis/occlusion in at least one organ or tissue; 4) aPL positivity.
- Note: Criterion 3 or 4 must be met (either one is sufficient).
Who cannot join
- History of severe drug allergy or a known allergic predisposition.
- Presence of, or suspected uncontrolled infection requiring treatment, including fungal, bacterial, viral, or other infections.
- Central nervous system (CNS) disorders, except for prior seizures, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, or CNS vasculitis attributable to the underlying disease, as determined by the investigator.
- Cardiac dysfunction deemed unable to tolerate study treatment (i.e., inadequate cardiac function at the investigator's discretion).
- Known congenital immunoglobulin deficiency.
- Presence of severe congenital structural malformations or syndromic birth defects (e.g., severe cardiovascular malformations, severe CNS malformations), or a confirmed diagnosis of a severe inherited metabolic disorder that, in the investigator's judgment, may significantly increase trial-related risk or interfere with compliance and interpretation of results.
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- History of malignancy within the past 5 years.
- End-stage renal disease.
- Evidence of certain chronic/active infections, including: HBsAg-positive, or HBcAb-positive with peripheral blood HBV DNA above the upper limit of detection; Anti-HCV antibody positive with detectable HCV RNA; HIV antibody positive; Positive syphilis test.
- Psychiatric illness or severe cognitive impairment.
- Participation in another clinical trial within 3 months prior to enrollment.
- Use of immunosuppressive agents with therapeutic effects on the underlying disease within five half-lives prior to enrollment, or use of biologic agents within 4 weeks prior to enrollment.
- Pregnant or planning pregnancy (females).
- Any other condition that, in the investigator's opinion, makes the participant unsuitable for enrollment in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Children's Hospital of Fudan University
Shanghai
Professor Qian Shen, +86 02164932829, shenqian@shmu.edu.cn
About this study
Official title: An Exploratory Clinical Study of the Safety and Efficacy of YTS109 Cell Injection in Children With Relapsed/Refractory Autoimmune Diseases
This exploratory, single-arm, open-label study will evaluate the safety and preliminary efficacy of YTS109 cell therapy in pediatric patients with relapsed/refractory autoimmune diseases, including systemic lupus erythematosus, diffuse systemic sclerosis, idiopathic inflammatory myopathies, and Sjögren's syndrome, as well as other eligible autoimmune diseases defined by the protocol eligibility criteria. Approximately 12 patients aged 5 to <18 years will be enrolled at Children's Hospital of Fudan University and will receive a single intravenous infusion of YTS109 cells. Dose escalation will follow a standard 3+3 design starting at 1.5 × 10^6 cells/kg. The primary objective is to assess the safety and preliminary efficacy of YTS109 cell therapy in this population. Secondary objectives include characterizing the pharmacokinetic and pharmacodynamic profiles of YTS109 cells. Primary endpoints include the type, severity, and frequency of adverse events, along with efficacy assessments.
Read the detailed description
Background: Autoimmune diseases (AIDs) comprise a heterogeneous group of disorders in which dysregulated immune responses target self-antigens, resulting in chronic inflammation and tissue damage. Although therapeutic options for AIDs have advanced in recent years, a subset of pediatric patients with relapsed or refractory disease continues to experience inadequate disease control, cumulative organ damage, and substantial treatment-related toxicity. B cells play a central role in the pathogenesis of many AIDs through autoantibody production, antigen presentation, and cytokine secretion. CD19-directed cellular immunotherapies, including CAR-T/related platforms, have emerged as promising approaches for severe autoimmune disease by enabling deep and potentially durable B-cell depletion, and therefore warrant further clinical evaluation in pediatric populations. YTS109 is a universal allogeneic CD19-targeting STAR-T cell therapy designed to efficiently eliminate CD19+ B cells and attenuate pathogenic autoimmune responses.
Design: This is a single-center, single-arm, prospective exploratory clinical trial designed to evaluate the safety profile, preliminary therapeutic efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of YTS109 cell therapy in children with relapsed/refractory autoimmune diseases. Eligible indications include systemic lupus erythematosus, diffuse systemic sclerosis, idiopathic inflammatory myopathies, Sjögren's syndrome, ANCA-associated vasculitis, and antiphospholipid syndrome, as defined by the protocol eligibility criteria. Approximately 12 patients aged 5 to <18 years will receive a single intravenous infusion of YTS109 cells, with dose escalation conducted using a standard 3+3 design starting at 1.5 × 10^6 cells/kg. The primary endpoint includes the type, severity, and frequency of adverse events (AEs), together with protocol-defined efficacy assessments. Secondary endpoints include PK/PD measures of YTS109 cell kinetics and immune reconstitution biomarkers. The study was approved by the Ethics Committee of Children's Hospital of Fudan University (Approval No. 2025-207). Written informed consent will be obtained from all participants and/or their legal guardians prior to study procedures.
- Conditions
- Systemic Lupus Erythematosus (SLE), Diffuse Systemic Sclerosis, Idiopathic Inflammatory Myopathies (IIMs), ANCA Associated Vasculitis (AAV), Antiphospholipid Syndrome (APS), Sjogren's Syndrome (SS)
- Being tested
- YTS109 cell
- Medical subject headings
- Lupus Erythematosus, Systemic, Scleroderma, Diffuse, Myositis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antiphospholipid Syndrome, Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YTS109 cellBiological
Single intravenous infusion of YTS109 cells; dose escalation per 3+3 design starting at 0.75×10^6 cells/kg.
YTS109 cellOther
Single intravenous infusion of YTS109 cells; dose escalation per 3+3 design starting at 0.75×10^6 cells/kg.
| Study group | Role | What they receive |
|---|---|---|
| YTS109 | Experimental | Single intravenous infusion of YTS109 cells; dose escalation per 3+3 design starting at 0.75×10^6 cells/kg. Receives: Biological: YTS109 cell; Other: YTS109 cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Safety assessments are conducted using the NCI-CTCAE version 5.0 standards.
Measured: 12weeks for safety measurements during the treatment assessment period
Efficacy outcomes for SLE
SLE Response index 4(SR-4) response: Min/Max Value: Not specife: a decrease in score indicates improvement: hicher scores indicate worse outcome
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Systemic Sclerosis
ACR-CRISS score (CRISS score ≥0.6 improvement, < 0.6 no improvement) and modified CRISS score (rCRISS score) (percentage of patients with at least 3 of the 5 core items of ACR-CRISS improved by a certain percentage (e.g. 25%, except FVC (5%))
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Inflammatory Myopathy
Total Improvement Score (TlS): Min/Max Value: Not specified; an increase in score indicates improvement, higher scores indicate better outcomes.
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Sjogren's Syndrome
Sjogren's tool for assessing response (STAR): Min/Max Value: Not specified: a decrease n score indicates improvement: higher scores indicate worse outcome
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Pediatric Vasculitis Activity Score Min/Max Value: 0 to 63: an increase in score indicates worsening condition. Higher cores indicate: Worse Outcome
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for antiphospholipid syndrome
Incidence of newly confirmed thrombotic events. New thrombotic events will be confirmed by objective imaging studies (e.g., Doppler ultrasonography, CT angiography, magnetic resonance imaging, or venography) and adjudicated according to the revised Sydney classification criteria for antiphospholipid syndrome.
Measured: 12 weeks for efficacy measurements during the treatment assessment period
Secondary outcomes (12)
Peak Plasma Concentration (Cmax) of YTS109
Cmax will be determined using validated quantitative PCR assay in peripheral blood samples.
Measured: 12 and 24 weeks
Time to Peak (Tmax) of YTS109
Time from infusion to observed Cmax (Days) . To evaluate the metabolic characteristics of YTS109
Measured: 12 and 24 weeks
Area under the plasma concentration versus time curve (AUC) of YTS109
Calculated using non-compartmental analysis. To evaluate the metabolic characteristics of YTS109
Measured: 12 and 24 weeks
Efficacy outcomes for SLE
SLE Response index 4 (SR-4) response: Min/Max Value: Not specific: a decrease in score indicates improvement. Higher scores indicate worse outcomes.
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Systemic Sclerosis
ACR-CRISS score (CRISS score ≥0.6 improvement, <0.6 no improvement) and modified CRISS score (rCRISS score) (percentage of patients with at least 3 of the 5 core items of ACR-CRISS improved by a certain percentage (e.g., 25%, except FVC (5%)).
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Inflammatory Myopathy
Total Improvement Score (TlS): Min/Max Value: Not specified; an increase in score indicates improvement, higher scores indicate better outcomes.
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Sjogren's Syndrome
Sjogren's tool for assessing response (STAR): Min/Max Value: Not specified: A decrease in score indicates improvement; higher scores indicate worse outcome
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Pediatric Vasculitis Activity Score Min/Max Value: 0 to 63: an increase in score indicates worsening condition. Higher cores indicate: Worse Outcome
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Efficacy outcomes for Antiphospholipid Syndrome
Evaluation of new thrombosis as an indicator of relapsed/refractory/catastrophic Antiphospholipid syndrome.
Measured: 24 weeks for efficacy measurements during the treatment assessment period
Change from baseline in serum IL-6 concentration (pg/ml)
Detect the IL-6 concentration by Enzyme-linked immunosorbent assay (ELISA)
Measured: 12 weeks and 24 weeks
Change from baseline in serum TNF-α concentration (pg/ml)
Detect the TNF-α concentration by Enzyme-linked immunosorbent assay (ELISA)
Measured: 12 weeks and 24 weeks
Change from baseline in peripheral CD19+ B cell count (cells/µL)
Peripheral CD19+ B cell counts will be quantified using flow cytometry in peripheral blood samples. Absolute B cell counts will be calculated based on total lymphocyte counts obtained from automated hematology analysis. Change from baseline will be calculated as the difference between post-infusion values and pre-infusion baseline levels.
Measured: 12weeks and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study startMar 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionJul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus Erythematosus (SLE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- China Immunotech (Beijing) Biotechnology Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07439029
- Sponsor's protocol ID
- IIT2025030
- Status last verified
- Feb 2026
- First submitted
- 8 Feb 2026
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Because this study involves a pediatric population and an investigational allogeneic cell therapy, individual participant data will not be shared publicly due to privacy, ethical, and institutional policy constraints. Study results will be reported in aggregate in publications and/or on ClinicalTrials.gov. De-identified data access may be considered only under exceptional circumstances, subject to institutional review and execution of a data use agreement.