A Single-Arm, Open-Label Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of CD19 CAR-T Cell Therapy in Patients With Moderate-to-Severe Refractory Pemphigus Vulgaris
This is an investigator-initiated, single-center, single-arm, open-label exploratory clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of autologous CD19 CAR-T cell therapy in patients with refractory pemphigus vulgaris.
∙ Participants must meet all of the following criteria:
• Ability to provide written informed consent.
• Age 18 to 70 years at screening, male or female.
• Diagnosis of pemphigus vulgaris confirmed by clinical presentation, histopathology, direct immunofluorescence (DIF), and positive anti-desmoglein 3 and/or anti-desmoglein 1 antibodies.
• Moderate-to-severe disease activity defined as Pemphigus Disease Area Index (PDAI) ≥ 15 at screening.
• Refractory pemphigus vulgaris is defined as inadequate response, disease relapse, or treatment dependence following systemic corticosteroids and rituximab-based therapy for at least 6 months, with persistent disease activity meeting at least one of the following criteria:
‣ Ongoing active disease with the appearance of new erythema, blisters, or erosions;
⁃ Persistently elevated anti-desmoglein 1 or anti-desmoglein 3 antibody titers \> 100 U/mL;
⁃ Inability to taper systemic corticosteroids to \< 20 mg/day prednisone equivalent (i.e., ≥ 4 tablets/day of standard prednisone dosing).
• Requirement for systemic therapy at screening due to active disease.
• Adequate vascular access for leukapheresis.
• Life expectancy greater than 6 months.
• Participants must have adequate organ function as defined below:
‣ Hematologic function: absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 50 × 10⁹/L, hemoglobin ≥ 80 g/L.
⁃ Renal function: Creatinine clearance ≥ 40 mL/min.
⁃ Hepatic function: ALT and AST ≤ 2.5 × upper limit of normal; total bilirubin ≤ 1.5 × upper limit of normal.
⁃ Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% with no clinically significant cardiac dysfunction.
⁃ Pulmonary function: Dyspnea ≤ Grade 1 (CTCAE v5.0) and oxygen saturation (SpO₂) ≥ 92% on room air.
⁃ Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal, with no clinically significant coagulopathy.
∙ 9\. No evidence of clinically significant active infection at baseline evaluation.
∙ 10\. Reproductive Criteria: Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test within 48 hours prior to initiation of lymphodepleting chemotherapy. Women of childbearing potential must agree to use effective contraception during study participation and for at least 12 months after CAR-T infusion. Male participants must agree to use effective contraception and avoid sperm donation during study participation and for at least 12 months after infusion.