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CAR-T cells in systemic B cell mediated autoimmune disease - CASTLE
EU CTIS ID: 2024-516819-24-00
What this study is testing
To assess the safety and toxicity of MB-CART19.1 in patients with active B-driven autoimmune disease (Systemic Lupus erythematosus [SLE], systemic sclerosis [SSc] and idiopathic inflammatory myopathy [IIM]).
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Adults aged ≥ 18 years at time of consent
- IIM subjects: Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, cyclophosphamide, 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
- 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 New York Heart Association [NYHA] III), ejection fraction (EF) > 30% and pulmonary (forced volume [FV] and diffusion capacity of the lungs [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 index <1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
You likely can't join if
- 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
See the full eligibility criteria
Who can join
- Adults aged ≥ 18 years at time of consent
- IIM subjects: Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, cyclophosphamide, 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
- 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 New York Heart Association [NYHA] III), ejection fraction (EF) > 30% and pulmonary (forced volume [FV] and diffusion capacity of the lungs [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 index <1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
- SLE subjects: Fulfilling the 2019 ACR/EULAR classification criteria of SLE
- SLE subjects: 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 history
- SLE subjects: 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 subjects: Insufficient response or intolerance/ contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, 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
- Must be able to adhere to the study visit schedule and other protocol requirements
- SSC subjects: Fulfilling the 2013 ACR/EULAR classification criteria of SSc
- SSC subjects: Positivity (+ or more) for at least one SSc-specific parameter (Scl70, RNA polymerase, Th/To, RP11/12, U3RNP autoantibodies) at screening or by documented medical history
- SSC subjects: 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 (C reactive protein [CRP] ≥ 6 mg/L, erythrocyte sedimentation rate [ESR] ≥ 28mm/h or platelet count ≥ 330 G/L), (iv) 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 subjects: Insufficient response or intolerance/ contraindication to at least 2 of the following treatments: mycophenolate mofetil, azathioprine, cyclophosphamide, nintedanib, methotrexate, rituximab. Insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point.
- IIM subjects: Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite IIM
- IIM subjects: Presence of active myositis in muscle biopsy or muscle MRI and/or signs of interstitial lung disease related to IIM
- IIM: Positivity (+ or more) for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma) at screening or by documented medical history
- IIM subjects: In patients with active myositis: Muscle weakness as defined 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
What rules you out
- 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 participation 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, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG)
- Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g., family members)
- Absolute neutrophil count (ANC) < 1.000/mm3, absolute lymphocyte count (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. human immunodeficiency virus (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
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.