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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат RD06-05 CAR-T Cell Injection
  CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Первичные конечные точки

• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• SLE (systemic lupus erythematosus) [Срок оценки: 2 years]
• AAV (ANCA-associated vasculitis) [Срок оценки: 2 years]
• AAV (ANCA-associated vasculitis) [Срок оценки: 2 years]
• IIM (idiopathic inflammatory myopathies) [Срок оценки: 2 years]
• SSc (systemic sclerosis) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07596680 · BHCT-RD06-05-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗