A Clinical Study of AFN50 in the Treatment of Autoimmune Diseases

Inclusion Criteria39

• 2 Age 18 to 69 years (inclusive), any gender. 1.3 Adequate bone marrow, coagulation, cardiac, pulmonary, hepatic, and renal function at screening:
• Bone Marrow Function:
• Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L (no use of granulocyte colony-stimulating factor (G-CSF) within 7 days before screening; for long-acting G-CSF, a 14-day interval is required); ② Haemoglobin (Hb) ≥90 g/L (no red blood cell transfusion within 14 days before screening; use of recombinant human erythropoietin is permitted); ③ Platelet count (PLT) ≥75 × 10⁹/L; absolute lymphocyte count (ALC) ≥0.5 × 10⁹/L.
• Coagulation Function: International normalised ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5 × the upper limit of normal (ULN).
• Cardiac Function: Left ventricular ejection fraction (LVEF) ≥50% as shown by echocardiography (ECHO).
• Pulmonary Function: Dyspnea ≤ CTCAE Grade 1, and pulse oxygen saturation (SpO₂) >92% on room air.
• Hepatic Function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 × ULN; total bilirubin ≤1.5 × ULN.
• Renal Function: Creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min, without requiring fluid support.
• 4 Baseline oxygen saturation >92% without supplemental oxygen. 1.5 Non-pregnant/non-lactating subjects. Women of childbearing potential must have a negative serum or urine pregnancy test report (women who have undergone surgical sterilisation or are postmenopausal for at least 2 years are not considered to be of childbearing potential) and must be willing to use contraception for 12 months following drug infusion.
• Relapsed/Refractory Systemic Lupus Erythematosus (SLE) 1.1 Meet the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria for SLE.
• 2 SLEDAI-2K score ≥6; if the score includes low complement and/or anti-dsDNA antibodies, the SLEDAI-2K clinical symptom score after excluding these two items must be ≥4.
• 3 History of SLE for at least 6 months, with disease remaining active or relapsing despite receiving stable standard therapy for at least 8 weeks (drug doses stable for the past 2 weeks).
• 4 Oral glucocorticoids (prednisone or equivalent) at a daily dose ≥7.5 mg and ≤30 mg; if combined with immunosuppressants, there is no minimum daily dose requirement.
• 5 At least two immunosuppressants (including hydroxychloroquine) have been used in a standardised manner.
• 6 Screening tests meet: positive serum antinuclear antibody (ANA), and/or positive anti-double-stranded DNA (anti-dsDNA) antibody, and/or hypocomplementemia (low C3 and/or low C4).
• 7 Definition of relapsed/refractory: Ineffective to conventional therapy or recurrence of disease activity after remission. Definition of conventional therapy: Stable use, alone or in combination, of the following drugs: non-steroidal anti-inflammatory drugs (NSAIDs), antimalarials, glucocorticoids, immunosuppressants (including but not limited to cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine), targeted drugs (including but not limited to belimumab, telitacicept, eculizumab, rituximab).
• Relapsed/Refractory Sjögren's Syndrome (SS) 2.1Meet the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren's Syndrome.
• 2 Definition of relapsed/refractory: Ineffective to conventional therapy or recurrence of disease activity after remission. Definition of conventional therapy: Use of glucocorticoids (≥1 mg/kg/day) and cyclophosphamide, plus any one or more of the following immunomodulatory drugs for >6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, telitacicept, etc.
• Refractory Myasthenia Gravis (MG) 3.1 Meet the diagnostic criteria for generalized myasthenia gravis as per the Chinese guidelines for the diagnosis and treatment of MG (2025 edition).
• 2 Myasthenia Gravis Foundation of America (MGFA) clinical classification: Type II, III, or IV.
• 3 Positive serology for acetylcholine receptor antibody (AChR-Ab), or muscle-specific tyrosine kinase antibody (MuSK-Ab), or low-density lipoprotein receptor-related protein 4 antibody (LRP4-Ab) at screening, or documented history of positive AChR-Ab, MuSK-Ab, or LRP4-Ab.
• 4 Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≥6, with ocular-related scores comprising less than 50% of the total score.
• 5 Myasthenia Gravis (QMG) score ≥8, with at least 4 individual item scores being ≥2 points.
• 6 Definition of refractory: Ineffective to conventional therapy or disease reactivation following remission.
• Relapsed/Refractory or Progressive Diffuse Cutaneous Systemic Sclerosis (dcSSc) 4.1 Meet the 2013 ACR classification criteria for systemic sclerosis, with diffuse cutaneous involvement.
• 2 Presence of interstitial lung disease: evidence of interstitial changes with ground-glass opacity on chest HRCT and forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (DLCO) <70% of predicted value on pulmonary function tests.
• 3 Definition of relapsed/refractory: Ineffective to conventional therapy or disease reactivation following remission.
• 4 Definition of conventional therapy: Use of glucocorticoids (≥1 mg/kg/day) and cyclophosphamide, plus any one or more of the following immunomodulatory drugs for >6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, telitacicept, etc.
• 5 Definition of progressive disease:
• Skin progression: Increase in modified Rodnan skin score (mRSS) >10%.
• Lung disease progression: Decrease in FVC by 10%, or decrease in FVC by 5% accompanied by a decrease in DLCO by 15% (OMERACT progression).
• Relapsed/Refractory or Progressive Idiopathic Inflammatory Myopathy (IIM) 5.1 Meet the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies (including DM, PM, ASS, and NM).
• 2 For patients with muscle involvement: Manual Muscle Testing-8 (MMT-8) score below 142 and at least two abnormal findings among the following five core measures (Physician Global Activity (PhGA), Patient Global Activity (PtGA) or extra-muscular disease activity score ≥2; Health Assessment Questionnaire (HAQ) total score ≥0.25; muscle enzyme levels 1.5 times the upper limit of normal).
• 3 Positive myositis antibodies. 5.4 Definition of relapsed/refractory: Ineffective to conventional therapy or recurrence of disease activity after remission. Definition of conventional therapy: Use of glucocorticoids (≥1 mg/kg/day) and cyclophosphamide, plus any one or more of the following immunomodulatory drugs for >6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, telitacicept, etc.
• 5 Definition of progressive disease: Rapidly progressive interstitial pneumonia occurring within a short period.
• Relapsed/Refractory Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV) 6.1 Meet the 2022 ACR/EULAR diagnostic criteria for ANCA-associated vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis.
• 2 Positive ANCA-related antibodies (MPO-ANCA or PR3-ANCA). 6.3 Birmingham Vasculitis Activity Score (BVAS) ≥15 points (total 63 points), indicating active vasculitis.
• 4 The BVAS assessment must include at least one major item, at least three minor items, or at least two renal items (hematuria and proteinuria).
• 5 Definition of relapsed/refractory: Ineffective to conventional therapy or recurrence of disease activity after remission. Definition of conventional therapy: Use of glucocorticoids (≥1 mg/kg/day) and cyclophosphamide, plus any one or more of the following immunomodulatory drugs for >6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, telitacicept, etc.