Ignite Creation Date:
2025-12-25 @ 4:53 AM
Ignite Modification Date:
2026-03-05 @ 10:45 AM
Study NCT ID:
NCT06347718
Status:
RECRUITING
Last Update Posted:
2025-09-30
First Post:
2023-12-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008180', 'term': 'Lupus Erythematosus, Systemic'}, {'id': 'D012595', 'term': 'Scleroderma, Systemic'}, {'id': 'D003882', 'term': 'Dermatomyositis'}, {'id': 'D017285', 'term': 'Polymyositis'}], 'ancestors': [{'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D009220', 'term': 'Myositis'}, {'id': 'D009135', 'term': 'Muscular Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Phase 1:\n\nEvaluating the safety of CAR-T-Cells in systemic autoimmune diseases with 8 patients\n\nPhase 2:\n\nEvaluating the efficiency of CAR-T-Cells in systemic autoimmune diseases with 16 patients'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 24}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-07-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2026-05-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-24', 'studyFirstSubmitDate': '2023-12-15', 'studyFirstSubmitQcDate': '2024-04-03', 'lastUpdatePostDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2024-04-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-05-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM).', 'timeFrame': 'up to d 28', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Clinical efficacy SSc', 'timeFrame': 'at week 24', 'description': 'Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease:\n\nSSc: No progression of interstitial lung disease with worsening of FVC1 (\\>10 percentage) or worsening of FVC1 (5-10 percentage) plus increase in respiratory symptoms or worsening of FVC1 (5-10 percentage) plus progression of high-resolution computed tomography changes after 24 weeks.'}, {'measure': 'Clinical efficacy SLE', 'timeFrame': 'at week 24', 'description': 'Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease:\n\nSLE: Fulfillment of DORIS remission criteria of SLE at week 24.'}, {'measure': 'Clinical efficacy DM', 'timeFrame': 'at week 24', 'description': 'Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease:\n\nDM: 2016 ACR/EULAR moderate or major response.'}, {'measure': 'Cellular response', 'timeFrame': 'up to week 24', 'description': '* amount of CAR T cells in the peripheral blood (cells/µl)\n* amount of B cells in the peripheral blood (cells/µl)\n* expansion of CAR T cells in the patient over time in cells/µl'}, {'measure': 'Serological response', 'timeFrame': 'up to week 24', 'description': 'Levels of respective serum autoantibodies at week 24 including incidence of sero-conversion measured in IE/ml\n\n* SLE: ANA-Titer, anti-dsDNA, anti-nucleosomes, anti-Sm, anti-cardiolipin IgG, C3 (mg/dl), C4 (mg/dl)\n* SSc: ANA-Titer, anti-SCL70, anti-RNA polymerase III, anti-topoisomerase\n* DM: ANA-Titer, anti-Mi2, anti-Tif1, anti-MDA5, anti-Jo1, anti-NXP2'}, {'measure': 'Success of IMP process', 'timeFrame': 'up to week 24', 'description': 'Success of the manufacturing process by GMP certification of the product (in percentage)'}, {'measure': 'Physicians Global Assessment to measure quality of life', 'timeFrame': 'up to week 24', 'description': "Physician's Global Assessment (PhGA) of disease activity (VAS 0-100mm), (0=no disease activity, 100=worst disease activity)"}, {'measure': "Patient's Global Assessment to measure quality of life", 'timeFrame': 'up to week 24', 'description': "Patient's Global Assessment (PtGA) of disease activity (VAS 0-100mm), (0=no disease activity, 100=worst disease activity)"}, {'measure': 'Health Assessment Questionnaire', 'timeFrame': 'up to week 24', 'description': 'Disease Index HAQ-DI (0-4 per question; 0=best function, 4=worst function)'}, {'measure': 'Functional Assessment of Chronic Illness Therapy', 'timeFrame': 'up to week 24', 'description': 'Fatigue with FACIT Fatigue questionaire, from 8-44, (8=worst, 44=best, serious fatigue defined \\<30)'}, {'measure': 'SLE-specific disease activity over time per subject', 'timeFrame': 'up to week 24', 'description': 'British Isles Lupus Assessment Group (BILAG) index Improvement of organ involvement according to BILAG A-E (A=severe organ involvement, E=mild organ involvement)'}, {'measure': 'SSc-specific disease activity over time per subject', 'timeFrame': 'up to week 24', 'description': 'modified Rodnan Skin Score (mRSS) points 0-4 according to skin stiffness (0=no thickening, 3=severe thickening)'}, {'measure': 'DM/PM-specific disease activity over time per subject', 'timeFrame': 'up to week 24', 'description': "Physician's global assessment (PhGA) of extramuscular activity 0-100mm (0=no disease activity, 100=worst disease activity)"}, {'measure': 'SLE-specific disease activity over time per subject', 'timeFrame': 'up to 24 weeks', 'description': 'Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) points 1-8 according to organ involvement 1=mild organ involvement, 8=severe organ involvement)'}, {'measure': 'DM/PM-specific disease activity over time per subject', 'timeFrame': 'up to 24 weeks', 'description': 'Manual Muscle Testing (MMT) points 0-150 (0=paraplegia, 150=full muscle strength)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Systemic Lupus Erythematosus', 'Systemic Sclerosis', 'Dermatomyositis', 'Polymyositis']}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* General:\n\n * Subjects must understand and voluntarily sign an informed consent form including written consent for data protection,\n * Adults aged ≥ 18 years at time of consent,\n * 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,\n * 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,\n * 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,\n * Must be able to adhere to the study visit schedule and other protocol requirements,\n * Double vaccination against SARS-CoV-2 or SARS-CoV-2 within the last 6 months.\n* SLE specific:\n\n * Fulfilling the 2019 ACR/EULAR classification criteria of SLE,\n * Positivity of anti-dsDNA (\\> 4 U/l), anti-histone (+ or more), anti-nucleosome (+ or more) or anti-Sm antibodies (+ or more),\n * 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),\n * 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.\n* SSc specific:\n\n * Fulfilling the 2013 ACR/EULAR classification criteria of SSc),\n * Positivity (+ or more) for at least one SSc-specific parameter (Scl70, RNA polymerase, Th/To, RP11/12, U3RNP autoantibodies),\n * 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,\n * 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.\n* DM/PM specific:\n\n * Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite DM or PM,\n * Presence of active myositis in muscle biopsy or muscle MRI and/or signs of interstitial lung disease related to DM/PM,\n * Positivity (+ or more) for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma),\n * 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,\n * 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.\n\nExclusion Criteria:\n\n* Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator\n* ANC \\< 1.000/mm3, ALC \\< 500/mm3 or hemoglobin \\< 8g/dl, absolute CD3+ T cell count \\< 100/μl,\n* Uncontrolled severe concomitant disease, such as cancer (except basal or squamous cell skin cancer) and diabetes mellitus,\n* Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), heart (NYHA IV, EF ≤ 30%) and pulmonary (FV and DLCO ≤ 30%) function,\n* 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,\n* Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy),\n* History of bone marrow/ hematopoietic stem cell or solid organ transplantation,\n* 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,\n* Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc,\n* Pregnant or lactating females,\n* Females who are intending to conceive during the study,\n* Known hypersensitivity to any drug components,\n* Malignancy in the last 5 years before screening,\n* Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis,\n* 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,\n* 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,\n* Subjects who possibly are dependent on the Sponsor, the Principal Investigator or other Investigators (e.g. family members).'}, 'identificationModule': {'nctId': 'NCT06347718', 'acronym': 'CASTLE', 'briefTitle': 'CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease', 'organization': {'class': 'INDUSTRY', 'fullName': 'Miltenyi Biomedicine GmbH'}, 'officialTitle': 'CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease', 'orgStudyIdInfo': {'id': 'CASTLE'}, 'secondaryIdInfos': [{'id': '2022-001366-35', 'type': 'EUDRACT_NUMBER'}, {'id': 'DRKS00032279', 'type': 'REGISTRY', 'domain': 'Deutsches Register Klinischer Studien (DRKS)'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Active dose', 'description': 'A prospective, open-label, non-randomized, single-dose interventional basket study.\n\nSingle 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.\n\nNo control intervention (e.g. another immunosuppressive therapy). Concomitant measures: Leukapheresis and lymphodepleting therapy for conditioning.', 'interventionNames': ['Drug: anti-CD19 CAR T cell therapy']}], 'interventions': [{'name': 'anti-CD19 CAR T cell therapy', 'type': 'DRUG', 'description': 'Single-dose', 'armGroupLabels': ['Active dose']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91054', 'city': 'Erlangen', 'state': 'Bavaria', 'status': 'RECRUITING', 'country': 'Germany', 'contacts': [{'name': 'Georg Schett, Prof. Dr.', 'role': 'CONTACT'}, {'name': 'Daniela Bohr, Dr.', 'role': 'CONTACT'}], 'facility': 'Universitätsklinikum Erlangen', 'geoPoint': {'lat': 49.59099, 'lon': 11.00783}}], 'centralContacts': [{'name': 'Georg Schett, Prof. Dr. med. univ.', 'role': 'CONTACT', 'email': 'georg.schett@uk-erlangen.de', 'phone': '+49 9131 85 32093'}, {'name': 'Daniela Bohr, Dr.med', 'role': 'CONTACT', 'email': 'daniela.bohr@uk-erlangen.de', 'phone': '+49 9131 85 32093'}], 'overallOfficials': [{'name': 'Georg Schett, Prof. Dr. med. univ.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Universitätsklinikum Erlangen'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Miltenyi Biomedicine GmbH', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}