NCT07596680尚未招募1 期
Clinical Study on the Safety, Efficacy and Pharmacokinetics of Universal CD19/BCMA-Targeted CAR-T Cell Injection in Patients With Autoantibody-Mediated Autoimmune Diseases
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 2
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 IIM
- •Severe rhabdomyolysis or CK ≥120×ULN at screening.
- •FVC ≤50% predicted or DLCO ≤40% predicted at screening.
- •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.
研究组 & 干预措施
RD06-05
Experimental
干预措施: RD06-05 CAR-T Cell Injection (Drug)
研究者
研究点 (2)
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