Clinical Study of AFN50 Injection in the Autoimmune Diseases

Обзор

This is an investigator-initiated trial designed to evaluate the safety, tolerability and primary efficacy of AFN50 injection for the treatment of autoimmune diseases.

Подробное описание

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.

Вмешательства

• Биопрепарат AFN50 injection
  Intravenous infusion therapy. AFN50 was developed using novel T-cell-targeted lipid nanoparticles (T-LNP) encapsulating mRNA encoding Chimeric Antigen Receptor.

Первичные конечные точки

• Adverse events [Срок оценки: 3 months]

Вторичные конечные точки (8)

• in vivo CAR T cell production [Срок оценки: Day-28 to 28 days]
• B cell ratios and counts in peripheral blood [Срок оценки: Day-28 to 12 months]
• Changes in the 2000 Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) relative to baseline in participants [Срок оценки: Day-28 to12 months]
• SLE Responder Index-4 (SRI-4) [Срок оценки: Day-28 to12 months]
• Changes in the Physician's Global Assessment (PGA) relative to baseline [Срок оценки: Day-28 to12 months]
• Proportion of participants achieving DORIS remission [Срок оценки: Day-28 to12 months]
• Proportion of participants achieving complete renal response (CRR) [Срок оценки: Day-28 to12 months]
• Proportion of participants achieving low disease activity status (LLDAS) [Срок оценки: Day-28 to12 months]

Критерии участия

Критерии включения

• Be able to understand and voluntarily sign the written informed consent form;
• Patients aged between 18 and 69 (inclusive), of any gender, diagnosed with SLE according to the 2019 EULAR/ACR SLE diagnostic criteria;
• 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);
• 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;
• Standardized treatment failure with hydroxychloroquine or at least two immunosuppressants;
• 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);
• 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;
• 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;

• Baseline oxygen saturation >92% without oxygen supplementation;
• 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.

Критерии исключения

• 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;
• Presence of other uncontrolled active infections;
• History of major organ transplantation (such as heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation;
• 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;
• History of live vaccine administration within the last 30 days;
• 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;
• Pregnant or breastfeeding women;
• Individuals with asthma, severe allergies;
• 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.
• Other conditions deemed inappropriate for participation in this clinical study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• First Affiliated Hospital of Anhui Medical University — Хэфэй

Идентификаторы

NCT: NCT07408336 · PJ-2025-12-57

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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