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

Early Phase 1Not Yet RecruitingNCT07596680

Nanjing Bioheng Biotech Co., Ltd.30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

SLE - Systemic Lupus Erythematosus Systemic Sclerosis ANCA Associated Vasculitis Idiopathic Inflammatory Myopathies

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.