Autoimmune Diseases
Conditions
Keywords
AFN50, SLE
Brief summary
This is an investigator-initiated trial designed to evaluate the safety, tolerability and primary efficacy of AFN50 injection for the treatment of autoimmune diseases.
Detailed description
This study is a prospective exploratory clinical trial in subjects with autoimmune diseases, mainly relapsing and refractory systemic lupus erythematosus. The objective is to evaluate the safety, tolerability, and primary efficacy of AFN50 injection in relapsing and refractory systemic lupus erythematosus.
Interventions
BIOLOGICALAFN50 injection
Intravenous infusion therapy. AFN50 was developed using novel T-cell-targeted lipid nanoparticles (T-LNP) encapsulating mRNA encoding Chimeric Antigen Receptor.
Sponsors
AlphaNa Bioscience Company Limited
The First Affiliated Hospital of Anhui Medical University
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. Be able to understand and voluntarily sign the written informed consent form; 2. Patients aged between 18 and 69 (inclusive), of any gender, diagnosed with SLE according to the 2019 EULAR/ACR SLE diagnostic criteria; 3. A history of SLE for at least 6 months, having used a stable standard treatment regimen for at least 8 weeks, with the dosage stable for 2 weeks, yet the disease remains active or has relapsed; Standard treatment refers to the stable use of the following drugs alone or in combination: non-steroidal anti-inflammatory drugs (NSAIDs), antimalarials, corticosteroids; 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); 4. Oral corticosteroids are prednisone (or equivalent drug) ≥7.5mg/day and ≤30mg/day. If used in combination with immunosuppressants, there is no minimum daily dose requirement; 5. Standardized treatment failure with hydroxychloroquine or at least two immunosuppressants; 6. Screening period tests meet: positive blood antinuclear antibody (ANA), and/or positive anti-double-stranded DNA (anti-dsDNA) antibodies, and/or hypocomplementemia (low C3 and/or C4); 7. Screening period SLEDAI-2K score ≥6 points. If scoring includes low complement and/or anti-ds-DNA antibodies, the score for SLEDAI-2K clinical symptoms (excluding low complement and/or anti-ds-DNA antibodies) should be ≥4 points; 8. Appropriate bone marrow, coagulation, cardiopulmonary, liver, and kidney functions. Bone marrow function: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L (no granulocyte colony-stimulating factor (G-CSF) administered within 7 days prior to screening; a 14-day interval required for long-acting G-CSF); Hemoglobin (Hb) ≥80 g/L (no red blood cell transfusion within 14 days prior to screening; recombinant human erythropoietin is permitted. For patients meeting the Hb ≥80 g/L inclusion criterion, red blood cell transfusion is allowed during treatment to maintain hemoglobin level at ≥80 g/L); Platelet Count (PLT) ≥50×10⁹/L, Absolute Lymphocyte Count (ALC) ≥0.8×10⁹/L. Coagulation function: International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤1.5 times the upper limit of normal (ULN). Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥40% as measured by echocardiography (ECHO). Pulmonary function: Dyspnea of ≤CTCAE Grade 1; pulse oxygen saturation (SpO2) \>92% under room air. Hepatic function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5×ULN; total bilirubin ≤1.5×ULN. Renal function: Creatinine clearance rate (calculated by the Cockcroft-Gault formula) ≥50 mL/min, without the need for fluid support; 9. Baseline oxygen saturation \>92% without oxygen supplementation; 10. Non-pregnant/non-lactating participants. Women of childbearing potential must have a negative serum or urine pregnancy test result (women who have undergone surgical sterilization or postmenopausal women for at least 2 years are not considered women of childbearing potential) and be willing to adopt contraceptive measures within 12 months after drug infusion.
Exclusion criteria
1. Individuals with positive Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb), and Hepatitis B virus (HBV) DNA positivity or titers above the detection threshold; those with positive Hepatitis C virus (HCV) antibodies and HCV RNA positivity or titers above the detection threshold; individuals with Human Immunodeficiency Virus (HIV) antibodies positivity, CMV DNA positivity or above the detection limit; those with positive syphilis antigen or antibodies; 2. Presence of other uncontrolled active infections; 3. History of major organ transplantation (such as heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation; 4. Receiving any mRNA-LNP product or other LNP medications within the past two years, and with a history of allergy to LNP and its components; 5. History of live vaccine administration within the last 30 days; 6. History of any of the following cardiovascular diseases within the last 6 months before screening: Class III or IV heart failure defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac diseases; 7. Pregnant or breastfeeding women; 8. Individuals with asthma, severe allergies; 9. In the investigator's judgment, the participate is unlikely to complete all protocol-required study visits or procedures, including follow-up visits or adherence to the study participation requirements. 10. Other conditions deemed inappropriate for participation in this clinical study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 3 months | Incidence and severity of AEs associated with AFN50 as assessed by CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| in vivo CAR T cell production | 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 to12 months | 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. |
| Proportion of participants achieving DORIS remission | Day-28 to12 months | Proportion of participants achieving DORIS (Definition Of Remission In SLE) remission after AFN50 administration. |
| Proportion of participants achieving complete renal response (CRR) | Day-28 to12 months | Proportion of participants achieving complete renal response (CRR) after AFN50 administration |
| Proportion of participants achieving low disease activity status (LLDAS) | Day-28 to12 months | Maintenance of LLDAS: The proportion of participants with SLE who remain in Lupus Low Disease Activity State at predefined study visits through the 12-month follow-up period. |
Countries
China
Contacts
CONTACTBeicheng SUN, Dr
CONTACTHuan ZHOU, Dr
Outcome results
None listed