Relapsed/Refractory Autoimmune Diseases
Conditions
Keywords
Autoimmune Diseases
Brief summary
This study is a single-arm, open-label, single-centre exploratory clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of AFN50 Injection in adult patients with B-cell-mediated refractory/replapased autoimmune diseases.
Detailed description
The study employs a "3+3" dose-escalation design with a total of 9-18 subjects enrolled. The objective is to evaluate the safety, tolerability, and primary efficacy of AFN50 injection in relapsing and refractory autoimmune disease. The primary endpoint is the incidence and severity of treatment-related adverse events, with a total follow-up period of approximately 24 months.
Interventions
BIOLOGICALAFN50 injection
Intravenous infusion therapy. AFN50 was developed using novel T-cell-targeted lipid nanoparticles (T-LNP) that encapsulate RNA encoding a Chimeric Antigen Receptor.
Sponsors
Beijing Boren Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
1\. General Inclusion Criteria 1.1 Must be capable of understanding and voluntarily providing written informed consent. 1.2 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. 1.4 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. Disease-Specific Inclusion Criteria： 1. 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. 1.2 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. 1.3 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). 1.4 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. 1.5 At least two immunosuppressants (including hydroxychloroquine) have been used in a standardised manner. 1.6 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). 1.7 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). 2. Relapsed/Refractory Sjögren's Syndrome (SS) 2.1Meet the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren's Syndrome. 2.2 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. 3. 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). 3.2 Myasthenia Gravis Foundation of America (MGFA) clinical classification: Type II, III, or IV. 3.3 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. 3.4 Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≥6, with ocular-related scores comprising less than 50% of the total score. 3.5 Myasthenia Gravis (QMG) score ≥8, with at least 4 individual item scores being ≥2 points. 3.6 Definition of refractory: Ineffective to conventional therapy or disease reactivation following remission. 4. Relapsed/Refractory or Progressive Diffuse Cutaneous Systemic Sclerosis (dcSSc) 4.1 Meet the 2013 ACR classification criteria for systemic sclerosis, with diffuse cutaneous involvement. 4.2 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. 4.3 Definition of relapsed/refractory: Ineffective to conventional therapy or disease reactivation following remission. 4.4 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. 4.5 Definition of progressive disease: 1. Skin progression: Increase in modified Rodnan skin score (mRSS) \>10%. 2. Lung disease progression: Decrease in FVC by 10%, or decrease in FVC by 5% accompanied by a decrease in DLCO by 15% (OMERACT progression). 5. 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). 5.2 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). 5.3 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. 5.5 Definition of progressive disease: Rapidly progressive interstitial pneumonia occurring within a short period. 6. 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. 6.2 Positive ANCA-related antibodies (MPO-ANCA or PR3-ANCA). 6.3 Birmingham Vasculitis Activity Score (BVAS) ≥15 points (total 63 points), indicating active vasculitis. 6.4 The BVAS assessment must include at least one major item, at least three minor items, or at least two renal items (hematuria and proteinuria). 6.5 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.
Exclusion criteria
1\. General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 3 months | The incidence and severity of adverse events determined to be related to AFN50 treatment, as assessed per CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In vivo CAR T cell generation | Day -28 to 28 days | The counts, proportions and sustained days of CAR-T cells in the peripheral blood |
| B cell ratios and counts in peripheral blood | Day -28 to 12 months | Assessment of the change of B cell ratios and counts in peripheral blood after AFN50 treatment |
| Changes in the 2000 Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) relative to baseline in participants | Day -28 through Month 12 | Assessment of Systemic Lupus Erythematosus Disease Activity Index 2000 from baseline to the month 12 follow-up visit. A total score can fall between 0 and 105, which determines changes in the disease activity of patients. |
| SLE Responder Index-4 (SRI-4) | Day-28 to12 months | Achievement of SRI-4 response at one or more scheduled study visits between baseline and the Month 12 follow-up. |
| Changes in the Physician's Global Assessment (PGA) relative to baseline | Day-28 to12 months | A total score can range from 0.0 to 3.0, with higher scores indicating more severe disease activity. |
Countries
China
Contacts
CONTACTYajing Zhang, Dr.
Outcome results
None listed