NCT06347718招募中1 期
CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM).
研究概览
简要总结
The investigational product is designed to effectively combat B cells in patients with autoimmune diseases. Autologous T cells enriched with CD4/CD8 are genetically engineered using a lentiviral vector to express chimeric antigen receptors (CARs) that target the CD19 antigen on the cell surface of B cells and their precursors. During treatment, patients undergo leukapheresis, lymophodepleting chemotherapy and administration of the expanded CD19-CAR-transduced T cells.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must understand and voluntarily sign an informed consent form including written consent for data protection,
- •Adults aged ≥ 18 years at time of consent,
- •Adequate renal (eGFR > 30 ml/min/m2), liver (no Child Pugh C), heart (at worst NYHA 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,
- •Must be able to adhere to the study visit schedule and other protocol requirements,
- •Double vaccination against SARS-CoV-2 or SARS-CoV-2 within the last 6 months.
- •SLE specific:
- •Fulfilling the 2019 ACR/EULAR classification criteria of SLE,
- •Positivity of anti-dsDNA (> 4 U/l), anti-histone (+ or more), anti-nucleosome (+ or more) or anti-Sm antibodies (+ or more),
- •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),
- •Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: hydroxychloroquine, mycophenolate mofetil, belimumab, methotrexate, rituximab, cyclophosphamide. Insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point.
- •SSc specific:
- •Fulfilling the 2013 ACR/EULAR classification criteria of SSc),
- •Positivity (+ or more) for at least one SSc-specific parameter (Scl70, RNA polymerase, Th/To, RP11/12, U3RNP autoantibodies),
- •Signs for fast progression including (i) disease duration ≤ 5 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,
- •Insufficient response or intolerance/ contraindication to at least 2 of the following treatments: mycophenolate mofetil, azathioprine, nintedanib, methotrexate, rituximab. Insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point.
- •DM/PM specific:
- •Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite DM or PM,
- •Presence of active myositis in muscle biopsy or muscle MRI and/or signs of interstitial lung disease related to DM/PM,
- •Positivity (+ or more) for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma),
- •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,
- •Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: mycophenolate mofetil, ciclosporin A, tacrolimus, methotrexate, rituximab, intravenous immunoglobulins. 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
- •ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8g/dl, absolute CD3+ T cell count < 100/μl,
- •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 the subject 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 guidelines must have been initiated prior to enrollment,
- •Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc,
- •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,
- •Subjects who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent,
- •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 participation or study agent administration, or may interfere with interpretation of results,
- •Subjects who possibly are dependent on the Sponsor, the Principal Investigator or other Investigators (e.g. family members).
研究组 & 干预措施
Active dose
Other
A prospective, open-label, non-randomized, single-dose interventional basket study.
Single intravenous infusion of a freshly prepared advanced therapy medicinal product (ATMP) from autologous and expanded T cells transduced ex vivo with a CD19-CAR construct.
No control intervention (e.g. another immunosuppressive therapy). Concomitant measures: Leukapheresis and lymphodepleting therapy for conditioning.
干预措施: anti-CD19 CAR T cell therapy (Drug)
结局指标
主要结局
To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM).
时间窗: up to d 28
Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell-associated neurotoxicity (ICANS) within the first 4 weeks after ATMP administration.
次要结局
- Clinical efficacy SSc(at week 24)
- Clinical efficacy SLE(at week 24)
- Clinical efficacy DM(at week 24)
- Cellular response(up to week 24)
- Serological response(up to week 24)
- Success of IMP process(up to week 24)
- Physicians Global Assessment to measure quality of life(up to week 24)
- Patient's Global Assessment to measure quality of life(up to week 24)
- Health Assessment Questionnaire(up to week 24)
- Functional Assessment of Chronic Illness Therapy(up to week 24)
- SLE-specific disease activity over time per subject(up to 24 weeks)
- SSc-specific disease activity over time per subject(up to week 24)
- DM/PM-specific disease activity over time per subject(up to 24 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
尚未招募
1 期
CAR-T Cells Targeting Autoimmune DiseasesAutoimmune DiseasesNCT05459870Shenzhen Geno-Immune Medical Institute30
招募中
1 期
CAR-T cells in systemic B cell mediated autoimmune disease - CASTLECTIS2024-516819-24-00niversitaetsklinikum Erlangen AöR24
招募中
1 期
CAR-T cells in SysTemic B celL mediated autoimmunE DiseaseSystemic sclerosisM32M33M34DermatopolymyositisSystemic lupus erythematosusDRKS00032279Friedrich-Alexander-Universität Erlangen-Nürnberg, Medizinische Fakultät24
尚未招募
不适用
A Study of CAR-T Cells Targeting Autoimmune DiseasesAutoimmune DiseasesNCT06661811Beijing Boren Hospital12
招募中
早期 1 期
CD19-BAFF CAR-T Cells Therapy for Patients With Autoimmune DiseasesAutoimmune DiseasesNCT06279923Zhejiang University45