CD19/BCMA-Targeted Universal CAR-T Cell Injection for the Treatment of Autoimmune Diseases

Korábbi kezelés

• General Exclusion Criteria (All Patients):
  • Coexisting autoimmune disease confounding disease activity/safety (stable ≥3 months may be eligible with approval).
  • Anti-CD20 mAb/T-cell engager within 3 months; CD19/BCMA-targeted therapy within 6 months (exception with CD19⁺ B-cell > LLN and approval).
  • Rapidly progressive glomerulonephritis (RPGN).
  • NYHA III/IV heart failure; severe cardiac disease within 12 months.
  • Severe CNS disease impairing compliance/assessments.
  • Malignancy history (except cured non-melanoma skin cancer/carcinoma in situ, disease-free ≥3 years).
  • Primary immunodeficiency.
  • Uncontrolled infection (uncomplicated UTI/upper respiratory infection permitted).
  • Positive HIV; positive HCV (except undetectable RNA); positive syphilis.
  • Positive HBsAg; positive HBcAb (except undetectable HBV DNA).
  • Positive EBV/CMV DNA/IgM at screening.
  • Active/recurrent tuberculosis.
  • Prior CAR-T or genetically modified immune cell therapy.
  • Live attenuated vaccine within 4 weeks before enrollment.
  • Hypersensitivity to cell therapy product components.
  • Tacrolimus hypersensitivity or ≥Grade 3 toxicity requiring hospitalization.
  • Other clinical trial participation within 30 days before screening.
  • Pregnant/breastfeeding; childbearing potential unwilling to use effective contraception.
  • Any other ineligible condition (investigator judgment).
• Exclusion Criteria for SLE
  • Active/unstable neuropsychiatric SLE requiring intervention within 90 days.
  • Anti-BAFF/APRIL therapy within required washout period; multiple NSAIDs within 14 days; inability to hold NSAIDs; intra-articular glucocorticoids within 6 weeks; immunosuppressants exceeding dose limits; hydroxychloroquine dose adjustment within 8 weeks; ACEI/ARB/SGLT2i adjustment within 4 weeks.
• Exclusion Criteria for AAV
  • Alveolar hemorrhage requiring invasive ventilation beyond screening.
  • Dialysis/plasmapheresis within 12 weeks.
  • Renal transplantation history.
  • Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion.
  • High-dose IV glucocorticoids within 4 weeks.
  • Oral glucocorticoids >60mg prednisone equivalent daily for >6 weeks.
  • Specific immunosuppressants/biologics within 4 weeks.
  • Concomitant strong CYP3A4 inducers.
• Exclusion Criteria for SSc
  • Significant respiratory disease other than ILD.
  • FVC <50% or DLCO <40% predicted at screening/baseline.
  • Lung transplantation listing/expected within 12 months.
  • Scleroderma renal crisis within 6 months.
  • Scleroderma-like disorders.
  • Prior chlorambucil, bone marrow transplantation, or total lymphoid irradiation.
• Exclusion Criteria for pSS
  • Active fibromyalgia interfering with assessment/requiring medication adjustment (stable permitted).
  • Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion.
  • High-dose glucocorticoids (≥60mg/day) within 4 weeks.

Laborértékek

• Exclusion Criteria for IIM
  • Severe rhabdomyolysis or CK ≥120×ULN at screening.
  • FVC ≤50% predicted or DLCO ≤40% predicted at screening.

• General Inclusion Criteria (All Patients)
  • Voluntarily provides written informed consent.
  • Age ≥18 and ≤70 years, any gender.
  • Adequate organ function:
  • ALT and AST ≤3×ULN; total bilirubin ≤2×ULN (excluding Gilbert syndrome).
  • Creatinine ≤1.5×ULN or creatinine clearance ≥40 mL/min.
  • Neutrophils ≥1×10⁹/L; hemoglobin ≥60 g/L; platelets ≥20×10⁹/L; lymphocytes >0.3×10⁹/L.
  • INR ≤1.5×ULN or PT ≤1.5×ULN.
  • Resting room-air SpO₂ ≥92%.
  • LVEF ≥50% on echocardiogram.
  • Negative serum or urine pregnancy test for females of childbearing potential at screening.
  • Highly effective contraception required from 28 days before lymphodepletion until 12 months after RD06-05 infusion for females; effective barrier contraception required from lymphodepletion until 12 months after RD06-05 infusion for males, with no sperm donation during the study.
• For SLE Patients
  • Diagnosis of SLE per 2019 EULAR/ACR or 2012 SLICC criteria.
  • Active disease despite ≥2 months of stable (≥2 weeks) treatment with glucocorticoids plus immunosuppressants and/or biologics; prednisone ≥7.5 mg/day or equivalent.
  • Positive ANA, anti-dsDNA antibody, and/or anti-Smith antibody at screening.
  • SLEDAI-2K >6 and clinical SLEDAI-2K ≥4 at screening. Patients with lupus nephritis (proteinuria >0.5 g/24h, UPCR >500 mg/g, or active urinary sediment) are exempt from clinical SLEDAI-2K requirement.
  • Physician Global Assessment (PGA) ≥1.0 (0-3 VAS) at screening.
• For SSc Patients
  • Diagnosis of SSc per 2013 ACR/EULAR criteria.
  • Diffuse cutaneous SSc at screening.
  • Active disease defined by at least one of: new SSc within 2 years; new/worsening skin or thoracic/abdominal involvement within 6 months; worsening skin thickening (mRSS ≥2); tendon friction rubs within 3 months; worsening respiratory symptoms with FVC decline ≥5% predicted or DLCO decline ≥10% predicted; or ILD progression on HRCT compared to 12 months prior.
  • Refractory or relapsing disease after >6 months of conventional therapy including glucocorticoids, cyclophosphamide, immunosuppressants, and/or biologics.
• For AAV Patients
  • Diagnosis of ANCA-associated vasculitis (MPA, GPA, EGPA) per 2022 ACR/EULAR criteria.
  • Positive MPO-ANCA or PR3-ANCA.
  • BVAS with at least 1 major item, 3 minor items, or 2 renal items.
  • Failure of standard of care: no remission after ≥4 months of glucocorticoids plus cyclophosphamide/rituximab; relapse after prior remission; or persistent active disease despite ≥6 months of SOC.
• For IIM Patients
  • Diagnosis of IIM (DM, ASS, IMNM) per 2017 ACR/EULAR criteria (probability ≥55%).
  • Active disease defined by ≥2 abnormal core measures, or active myositis on muscle MRI, or active inflammation on muscle biopsy within 16 weeks.
  • Positive myositis-specific autoantibodies.
  • Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics.
• For pSS Patients
  • Diagnosis of primary Sjögren's syndrome per 2016 ACR/EULAR criteria.
  • Positive anti-SSA/Ro antibody.
  • ESSDAI ≥6 at screening.
  • Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics.