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

Clinical Study on the Safety, Efficacy and Pharmacokinetics of Universal CD19/BCMA-Targeted CAR-T Cell Injection in Patients With Autoantibody-Mediated Autoimmune Diseases

This is a single-arm, open-label, investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RD06-05 in patients with autoantibody-mediated autoimmune diseases. The enrolled population consists of patients with active autoimmune diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ANCA-associated vasculitis (AAV), idiopathic inflammatory myopathies (IIM), Sjögren's syndrome (SS), among others.

The CAR-T cell dose used in this study is 6×10⁶ CAR⁺ T cells/kg. Six subjects will be enrolled for each indication, with a total of 30 subjects to be enrolled.

Inclusion Criteria

1. General Inclusion Criteria (All Patients)

   1. Voluntarily provides written informed consent.

   2. Age ≥18 and ≤70 years, any gender.

   3. 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.

   4. Negative serum or urine pregnancy test for females of childbearing potential at screening.

   5. 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.

2. For SLE Patients

   1. Diagnosis of SLE per 2019 EULAR/ACR or 2012 SLICC criteria.
   2. Active disease despite ≥2 months of stable (≥2 weeks) treatment with glucocorticoids plus immunosuppressants and/or biologics; prednisone ≥7.5 mg/day or equivalent.
   3. Positive ANA, anti-dsDNA antibody, and/or anti-Smith antibody at screening.
   4. 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.
   5. Physician Global Assessment (PGA) ≥1.0 (0-3 VAS) at screening.

3. For SSc Patients

   1. Diagnosis of SSc per 2013 ACR/EULAR criteria.
   2. Diffuse cutaneous SSc at screening.
   3. 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.
   4. Refractory or relapsing disease after >6 months of conventional therapy including glucocorticoids, cyclophosphamide, immunosuppressants, and/or biologics.

4. For AAV Patients

   1. Diagnosis of ANCA-associated vasculitis (MPA, GPA, EGPA) per 2022 ACR/EULAR criteria.
   2. Positive MPO-ANCA or PR3-ANCA.
   3. BVAS with at least 1 major item, 3 minor items, or 2 renal items.
   4. 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.

5. For IIM Patients

   1. Diagnosis of IIM (DM, ASS, IMNM) per 2017 ACR/EULAR criteria (probability ≥55%).
   2. Active disease defined by ≥2 abnormal core measures, or active myositis on muscle MRI, or active inflammation on muscle biopsy within 16 weeks.
   3. Positive myositis-specific autoantibodies.
   4. Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics.

6. For pSS Patients

   1. Diagnosis of primary Sjögren's syndrome per 2016 ACR/EULAR criteria.
   2. Positive anti-SSA/Ro antibody.
   3. ESSDAI ≥6 at screening.
   4. Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics.

Exclusion Criteria:

1. General Exclusion Criteria (All Patients):

   1. Coexisting autoimmune disease confounding disease activity/safety (stable ≥3 months may be eligible with approval).
   2. Anti-CD20 mAb/T-cell engager within 3 months; CD19/BCMA-targeted therapy within 6 months (exception with CD19⁺ B-cell > LLN and approval).
   3. Rapidly progressive glomerulonephritis (RPGN).
   4. NYHA III/IV heart failure; severe cardiac disease within 12 months.
   5. Severe CNS disease impairing compliance/assessments.
   6. Malignancy history (except cured non-melanoma skin cancer/carcinoma in situ, disease-free ≥3 years).
   7. Primary immunodeficiency.
   8. Uncontrolled infection (uncomplicated UTI/upper respiratory infection permitted).
   9. Positive HIV; positive HCV (except undetectable RNA); positive syphilis.
   10. Positive HBsAg; positive HBcAb (except undetectable HBV DNA).
   11. Positive EBV/CMV DNA/IgM at screening.
   12. Active/recurrent tuberculosis.
   13. Prior CAR-T or genetically modified immune cell therapy.
   14. Live attenuated vaccine within 4 weeks before enrollment.
   15. Hypersensitivity to cell therapy product components.
   16. Tacrolimus hypersensitivity or ≥Grade 3 toxicity requiring hospitalization.
   17. Other clinical trial participation within 30 days before screening.
   18. Pregnant/breastfeeding; childbearing potential unwilling to use effective contraception.
   19. Any other ineligible condition (investigator judgment).

2. Exclusion Criteria for SLE

   1. Active/unstable neuropsychiatric SLE requiring intervention within 90 days.
   2. 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.

3. Exclusion Criteria for AAV

   1. Alveolar hemorrhage requiring invasive ventilation beyond screening.
   2. Dialysis/plasmapheresis within 12 weeks.
   3. Renal transplantation history.
   4. Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion.
   5. High-dose IV glucocorticoids within 4 weeks.
   6. Oral glucocorticoids >60mg prednisone equivalent daily for >6 weeks.
   7. Specific immunosuppressants/biologics within 4 weeks.
   8. Concomitant strong CYP3A4 inducers.

4. Exclusion Criteria for IIM

   1. Severe rhabdomyolysis or CK ≥120×ULN at screening.
   2. FVC ≤50% predicted or DLCO ≤40% predicted at screening.

5. Exclusion Criteria for SSc

   1. Significant respiratory disease other than ILD.
   2. FVC <50% or DLCO <40% predicted at screening/baseline.
   3. Lung transplantation listing/expected within 12 months.
   4. Scleroderma renal crisis within 6 months.
   5. Scleroderma-like disorders.
   6. Prior chlorambucil, bone marrow transplantation, or total lymphoid irradiation.

6. Exclusion Criteria for pSS

   1. Active fibromyalgia interfering with assessment/requiring medication adjustment (stable permitted).
   2. Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion.
   3. High-dose glucocorticoids (≥60mg/day) within 4 weeks.