CAR-T cells in systemic B cell mediated autoimmune disease - CASTLE

Phase 1

Recruiting

Conditions: Systemic Sclerosis, Dermatomyositis/Polymyositis, Systemic Lupus Erythematosus
MedDRA version: 21.1Level: PTClassification code: 10042945Term: Systemic lupus erythematosus Class: 100000004859
MedDRA version: 21.0Level: LLTClassification code: 10042953Term: Systemic sclerosis Class: 10028395
MedDRA version: 20.0Level: PTClassification code: 10012503Term: Dermatomyositis Class: 100000004858
MedDRA version: 20.0Level: PTClassification code: 10036102Term: Polymyositis Class: 100000004859
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: CTIS2024-516819-24-00

Lead Sponsor: niversitaetsklinikum Erlangen AöR

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

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 poin

Exclusion Criteria

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