Scleroderma Clinical Trials

• Understand trial procedures and methods, voluntarily sign the informed consent form .

• Age ranges from 18 to 65 years old (including threshold), regardless of gender.

• Positive expression of CD19 on peripheral blood B cells determined by flow cytometry.

• Bone marrow function: neutrophil count ≥ 1.5 × 10\^9/L, lymphocyte count ≥ 0.8 × 10\^9/L, hemoglobin ≥ 90 g/L, platelet ≥ 100 × 10\^9/L. Blood transfusion and growth factors must not be used within 14 days prior to screening to meet the above requirements.

• Coagulation function: international normalized ratio or activated partial thromboplastin time ≤ 1.5× upper limit of normal range (ULN).

• Cardiopulmonary function: left ventricular ejection fraction ≥ 50% on echocardiography; for lung function, dyspnea ≤Grade 1 of the NCI-CTCAE version 5.0 standards when breathing room air, and pulse oximetry ≥ 92%.

• Liver function: alanine aminotransferase ≤ 1.5 × ULN, aspartate aminotransferase ≤ 1.5 × ULN, total bilirubin ≤ 1.5 × ULN (total bilirubin at least ≤ 3.0 mg/dL in patients with Gilbert syndrome).

• Renal function: creatinine clearance (by Cockcroft-Gault formula) ≥ 50 mL/min.

• Criteria for SLE：

‣ Meet the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria for SLE;

⁃ SLEDAI-2000 score \> 6 in the moderate to severe active phase of the disease;

⁃ And have at least one British Isles Lupus Assessment Group (BILAG-2004) grade A (severe manifestation) or two grade B (moderate manifestation) organ scores, or both.

⁃ Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (Above 1 mg/kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab, belimumab, and telitacicept.

• Criteria for Sjögren's syndrome:

‣ Meet the 2002 AECG criteria for primary Sjögren's syndrome or the 2016 ACR/EULAR classification criteria;

⁃ Disease activity ESSDAI ≥ 6;

⁃ Anti-SSA/Ro antibody positive;

⁃ Definition of relapse/refractory: disease activity that is ineffective to conventional treatment for more than 6 months or recurs after response. Definition of conventional treatment is use of glucocorticoids and cyclophosphamide, and any of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and telitacicept.

• Criteria for systemic sclerosis:

‣ Meet the 2013 ACR classification criteria for systemic sclerosis and meet diffuse manifestations;

⁃ Combined interstitial pneumonia: interstitial changes with ground-glass exudate detected by chest high-resolution computed tomography (HRCT);

‣ Needs to be met c. or d.:

⁃ Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (Above 0.5 mg/kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.

⁃ Meet the definition of progression: 1) Definition of skin progression: mRSS increases b \> 25%; 2) Definition of lung disease progression: FVC decreased by 10%, or FVC decreased by 5% and DLCO decreased by 15%.

• Criteria for inflammatory myopathy:

‣ The classification criteria for inflammatory myopathy comply with the 2017 EULAR/ACR (including DM, PM, ASS and NM);

⁃ For patients with muscle involvement, the MMT-8 score is less than 142 and abnormalities are found in at least two of the following five core measures (PhGA, PtGA, or extramuscular disease activity score ≥ 2 points; total HAQ score ≥ 0.25; muscle enzyme level is 1.5 times upper limit of normal);

⁃ Myositis antibody positive;

‣ Needs to be met d. or e.:

⁃ Definition of relapse/refractory: Failure of conventional treatment or relapse of disease activity after response. Definition of conventional treatment: Use of glucocorticoids (greater than 1 mg/kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.

⁃ Meet the definition of progression: Interstitial pneumonia progresses rapidly over a short period of time.

• Criteria for ANCA-associated vasculitis:

‣ Meet the diagnostic criteria for ANCA-associated vasculitis in the 2022 ACR/EULAR, including microscopic polyangiitis, granulomatous polyangiitis, eosinophilic granulomatosis with polyangiitis;

⁃ ANCA-related antibody positive (MPO-ANCA or PR3-ANCA positive);

⁃ Birmingham Vasculitis Activity Scale (BVAS) ≥ 15 points (out of a total of 63 points), indicating activity of vasculitis;

⁃ Must have at least one major item, at least three minor items, or at least two renal items, hematuria and proteinuria, in the BVAS assessment;

⁃ Definition of relapse/refractory: Failure of conventional treatment or relapse of disease activity after response. Definition of conventional treatment: Use of glucocorticoids (greater than 1 mg/kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.