2024-516819-24-00招募中2 期
CAR-T cells in systemic B cell mediated autoimmune disease - CASTLE
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell Associated Neurotoxicity Syndrome (ICANS) within the first 4 weeks after ATMP administration
研究概览
简要总结
To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Adults aged ≥ 18 years at time of consent
- •SSC: Fulfilling the 2013 ACR/EULAR classification criteria of SSc
- •SSC: Positivity (+ or more) for at least one SSc-specific parameter (Scl70, RNA polymer-ase, Th/To, RP11/12, U3RNP autoantibodies) at screening or by documented medical history
- •SSC: Signs for fast progression including (i) disease duration ≤ 7 years (from onset of first non-Raynaud manifestation), (ii) mRSS score 10-35 at screening, (iii) elevated acute phase reactant levels (CRP ≥ 6 mg/L, ESR ≥ 28mm/h or platelet count ≥ 330 G/L), (iii) mRSS increase ≥ 3 units or involvement of one new body area or mRSS increase ≥ 2 units in one body area or ≥ 1 tendon friction rub over 6 months
- •SSC: Insufficient response or intolerance/ contraindication to at least 2 of the following treatments: mycophenolate mofetil, azathioprine, cyclophosphamide, nintedanib, methotrexate, rituximab
- •DM/PM: Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite DM or PM
- •DM/PM: Presence of active myositis in muscle biopsy or muscle MRI and/or signs of interstitial lung disease related to DM/PM
- •DM/PM: Positivity (+ or more) for at least one myositis-specific antibody (aminoacyl tRNA syn-thetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma) at screening or by documented medical history
- •DM/PM: In patients with active myositis: Muscle weakness as define by MMT < 142 and 2 of the following criteria: VAS patients Global ≥2cm, VAS physician Global ≥ 2cm, HAQ > 0.25, at least one muscle enzyme > 1.3 times upper limit of normal, VAS global extra muscular activity ≥ 2cm
- •DM/PM: Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, cyclophosphamide, mycophenolate mo-fetil, ciclosporin A, tacrolimus, methotrexate, rituximab, intravenous immunoglobulins
- •Subjects must understand and voluntarily sign an informed consent form including written consent for data protection
- •Adequate renal (eGFR > 30 ml/min/m2), liver (no Child Pugh C), heart (at worst NY-HA III, EF > 30%) and pulmonary (FV and DLCO ≥ 30%) function
- •Male subjects unless surgically sterile, must agree to use two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) until 12 months after dosing of the IMP
- •Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening and must agree to use a highly effective contraceptive method (Pearl in-dex <1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
- •SLE: Fulfilling the 2019 ACR/EULAR classification criteria of SLE
- •SLE: Positivity of anti-dsDNA (> 4 U/l), anti-histone (+ or more), anti-nucleosome (+ or more) or anti-Sm antibodies (+ or more) at screening or by documented medical histo-ry
- •SLE: Active disease at screening, defined as ≥ 1 organ system with a British Isles Lupus Assessment (BILAG) A score (severe disease activity) or ≥ 2 organ systems with a BILAG B score (moderate disease activity)
- •SLE: Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, hydroxychloroquine, mycophenolate mo-fetil, belimumab, methotrexate, rituximab, cyclophosphamide. Insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point
排除标准
- •Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator
- •Pregnant or lactating females
- •Females who are intending to conceive during the study
- •Known hypersensitivity to any drug components
- •Malignancy in the last 5 years before screening
- •Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis
- •Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participa-tion or study agent administration, or may interfere with interpretation of results
- •Subjects who are younger than 18 years or are incapable to understand the aim, im-portance and consequences of the study and to give legal informed consent
- •Subjects who possibly are dependent on the Sponsor, the Principal Investigator or In-vestigator (e.g. family members)
- •ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8g/dl
- •Uncontrolled severe concomitant disease, such as cancer (except basal or squamous cell skin cancer) and diabetes mellitus
- •Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), heart (NYHA IV, EF ≤ 30%) and pulmonary (FV and DLCO < 30%) function
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- •Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy)
- •History of bone marrow/ hematopoietic stem cell or solid organ transplantation
- •Any concomitant severe active infection, e.g. HIV, hepatitis B or C, SARS-CoV 2 (COVID 19), or active tuberculosis as defined by a positive Quantiferon TB-test. If presence of latent tuberculosis is established then treatment according to local guide-lines must have been initiated prior to enrollment
- •Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc
结局指标
主要结局
Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell Associated Neurotoxicity Syndrome (ICANS) within the first 4 weeks after ATMP administration
Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell Associated Neurotoxicity Syndrome (ICANS) within the first 4 weeks after ATMP administration
次要结局
未报告次要终点
研究者
Clinical Trial Desk
Scientific
Miltenyi Biomedicine GmbH
研究点 (1)
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