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| Name | Class |
|---|---|
| The First Affiliated Hospital of Anhui Medical University | OTHER |
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This study evaluates the safety and efficacy of YTS109 cells in adults with relapsed/refractory autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), including LN and SLE-ITP, Sjogren's Syndrome, etc. Aproximately 18 patients aged 18-65 will receive a single infusion of YTS109 cells. The dose groups are set to commence at 3×10⁶ STAR -T cells/kg, employing a 3+3 escalation principle for dose titration. The primary objective of this study is to evaluate the safety of YTS109 cells therapy in treating recurrent/refractory autoimmune diseases, while the secondary objectives are to assess the efficacy of YTS109 cells as well as their pharmacokinetic and pharmacodynamic characteristics. The primary endpoint is observations of types, severity, and frequency of adverse events (AEs) and efficacy assessment. This single-arm, open-label trial will enroll patients across The First Affiliated Hospital of Anhui Medical University.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| YTS109 cell | Experimental | Subjects will receive YTS109 cell once in this study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YTS109 cell | Drug | Subjects will receive a single infusion of YTS109 cells. The dose groups are set to commence at 3×10⁶ STAR-T cells/kg, employing a 3+3 escalation principle for dose titration. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events |
| The efficacy endpoint evaluation for 2, 4, 8, 12 weeks, AEs observation will be follow-up for 24 weeks. The observation period is extended to 52 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy Evaluation in relapsed/refractory autoimmune diseases | The proportion of subjects achieving complete response (CR), partial response (PR), or other responses at week 12. | 2, 4, 8, 12 weeks, and the observation will continue until 24 to 52 weeks post-treatment. |
| Maximum Plasma Concentration of YTS109 (Cmax) |
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Inclusion Criteria:
Common inclusion criteria:
1. Age ranges from 18 to 65 years old (including threshold), regardless of gender.
2. Essential Organ Function Criteria:
4. Voluntary participation with signed informed consent and compliance.
Specific inclusion criteria:
Relapsing and refractory systemic lupus erythematosus:
Refractory Lupus Nephritis:
Refractory SLE-Associated Immune Thrombocytopenia:
Relapsing and refractory Sjögren's syndrome:
Relapsing and refractory Sjogren's Syndrome:
1. Meeting the 2013 American College of Rheumatology (ACR) classification criteria for systemic sclerosis; 2. Testing positive for systemic sclerosis-related antibodies; 3. Presenting with diffuse cutaneous sclerosis or active interstitial lung disease (as indicated by ground-glass opacities on high-resolution computed tomography, HRCT); 4. Definition of relapsing and refractory condition: Persistence of disease activity or recurrence of disease activity after remission, despite undergoing conventional treatment for more than six months. Definition of conventional treatment: Administration of glucocorticoids and cyclophosphamide, in combination with any one or more of the following immunomodulatory agents: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents including rituximab, belimumab, telitacicept, etc.; 5. Definition of progressive condition: Demonstrating rapid skin progression (an increase in modified Rodnan skin score, mRSS, of >25%) or pulmonary disease progression (a 10% decrease in forced vital capacity, FVC, or a >5% decrease in FVC accompanied by a 15% decrease in diffusion capacity for carbon monoxide, DLCO).
Note: Meeting either criterion 4 or 5 is sufficient.
Relapsing and refractory Inflammatory Myopathy:
1. Meeting the 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for inflammatory myopathies (including dermatomyositis, DM; polymyositis, PM; antisynthetase syndrome, ASS; and necrotizing myopathy, NM); 2. Testing positive for myositis-specific antibodies; 3. For patients with muscle involvement, having a Manual Muscle Testing-8 (MMT-8) score below 142 and at least two abnormal findings among the following five core measures (Physician's Global Assessment, PhGA; Patient's Global Assessment, PtGA, or extra-muscular disease activity score ≥ 2 points; Health Assessment Questionnaire, HAQ, total score ≥ 0.25; muscle enzyme levels 1.5 times the upper limit of normal range); or having an MMT-8 score ≥ 142 but presenting with active interstitial lung disease (as indicated by ground-glass opacities on high-resolution computed tomography, HRCT); 4. Definition of relapsing and refractory condition: Persistence of disease activity or recurrence of disease activity after remission, despite undergoing conventional treatment for more than six months. Definition of conventional treatment: Administration of glucocorticoids and cyclophosphamide, in combination with any one or more of the following immunomodulatory agents: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents including rituximab, belimumab, telitacicept, etc.; 5. Definition of progressive condition: Demonstrating worsening myositis or rapidly progressive interstitial pneumonia.
Note: Meeting either criterion 4 or 5 is sufficient.
Relapsing and refractory Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis:
1. Meeting the 2022 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) diagnostic criteria for ANCA-associated vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis.
2. Testing positive for ANCA-related antibodies (either MPO-ANCA or PR3-ANCA positive).
3. A Birmingham Vasculitis Activity Score (BVAS) of ≥15 points (out of a total of 63 points), indicating active vasculitis.
4. Definition of relapsing/refractory condition: Persistence of disease activity or recurrence of disease activity after remission, despite undergoing conventional treatment for more than six months. Definition of conventional treatment: Administration of glucocorticoids and cyclophosphamide, in combination with any one or more of the following immunomodulatory agents: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents including rituximab, belimumab, telitacicept, etc.
Relapsing and refractory Antiphospholipid Syndrome:
Note: Meeting either criterion 3 or 4 is sufficient.
Exclusion Criteria:
- Subjects who meet any of the following exclusion criteria will not be admitted to the study:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Huan Zhou | Contact | 86-13665527160 | zhouhuanbest@vip.163.com | |
| Zhili Wu | Contact | 86-13075536703 | 13075536703@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Anhui Medical University | Recruiting | Hefei | Anhui | China |
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To evaluate the metabolic characteristics of YTS109 |
| The detections will be conducted on day0, 4, 7, 10, and weeks 2, 3, 4, 8, 12. Then, observation will continue until 12 to 24 weeks post-treatment. |
| Area Under the Plasma Concentration-Time Curve (AUC) of YTS109 | To evaluate the metabolic characteristics of YTS109 | The detections will be conducted on day0, 4, 7, 10, and weeks 2, 3, 4, 8, 12. Then, observation will continue until 12 to 24 weeks post-treatment. |
| Time to Reach Maximum Plasma Concentration (Tmax) of YTS109 | To evaluate the metabolic characteristics of YTS109 | The detections will be conducted on day0, 4, 7, 10, and weeks 2, 3, 4, 8, 12. Then, observation will continue until 12 to 24 weeks post-treatment. |
| Cytokines Concentration Level Change | Evaluate the Pharmacodynamic (PD) effects of YTS109 cells | The detections will be conducted on day0, 4, 7, 10, and weeks 2, 3, 4, 8, 12. Then, observation will continue until 24 to 52 weeks post-treatment. |
| The reconstitution of B cell in peripheral blood | Changes in B cells quantification and phenotypic in peripheral blood | The detections will be conducted on day0, 4, 7, 10, and weeks 2, 3, 4, 8, 12. Then, observation will continue until 24 to 52 weeks post-treatment. |
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D008181 | Lupus Nephritis |
| D012595 | Scleroderma, Systemic |
| D009220 | Myositis |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| D016736 | Antiphospholipid Syndrome |
| D012008 | Recurrence |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D012871 | Skin Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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