AUTOLOGOUS T-CELLS TRANSDUCED WITH LENTIVIRAL VECTOR EXPRESSING A CHIMERIC ANTIGEN RECEPTOR DIRECTED AGAINST CD19 for Systemic sclerosis|Idiopathic inflammatory myopathy|Systemic lupus erythematosus

Inclusion criteria

• {"criterion_text":"- Adults aged ≥ 18 years at time of consent\n- 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\n- Subjects must understand and voluntarily sign an informed consent form including written consent for data protection\n- 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\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 index <1) starting from the time of signing the ICF and for 12 months after dosing of the IMP\n- SLE subjects: Fulfilling the 2019 ACR/EULAR classification criteria of SLE\n- 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\n- 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)\n- 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\n- Must be able to adhere to the study visit schedule and other protocol requirements\n- SSC subjects: Fulfilling the 2013 ACR/EULAR classification criteria of SSc\n- 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\n- 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\n- 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.\n- IIM subjects: Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite IIM\n- IIM subjects: Presence of active myositis in muscle biopsy or muscle MRI and/or signs of interstitial lung disease related to IIM\n- 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\n- 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"}

Exclusion criteria

• {"criterion_text":"- Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator\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- 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 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)\n- Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g., family members)\n- Absolute neutrophil count (ANC) < 1.000/mm3, absolute lymphocyte count (ALC) < 500/mm3 or hemoglobin < 8g/dl\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 he/she 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. 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\n- Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Grading of severity graded 0-4; assessed within the first 4 weeks after ATMP administration (incidence and severity grading as stated)."}

Secondary endpoints

• {"endpoint_text":"- •\tOverall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: -\tSLE: Fulfillment of DORIS remission criteria of SLE at week 24.","definition_or_measurement_approach":"ORR at week 24 measured by disease-specific validated composite indexes; for SLE defined as Fulfillment of DORIS remission criteria at week 24."}
• {"endpoint_text":"- •\tOverall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: -\tSSc: No progression of interstitial lung disease with worsening of forced vital capacity (FVC)1 (>10%) or worsening of FVC1 (5-10%) plus increase in respiratory symptoms or worsening of FVC1 (5-10%) plus progression of high-resolution computed tomography changes after 24 weeks.","definition_or_measurement_approach":"ORR at week 24 per SSc-specific criteria: no progression of ILD as defined by FVC changes and/or HRCT changes after 24 weeks."}
• {"endpoint_text":"- •\tOverall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: -\tIIM: 2016 ACR/EULAR Moderate or Major Response. No progression of interstitial lung disease with worsening of FVC1 (>10%) or worsening of FVC1 (5-10%) plus increase in respiratory symptoms or worsening of FVC1 (5-10%) plus progression of high-resolution computed tomography changes after 24 weeks.","definition_or_measurement_approach":"ORR at week 24 for IIM defined as 2016 ACR/EULAR Moderate or Major Response; ILD progression criteria as described (FVC and HRCT changes)."}
• {"endpoint_text":"- •\tDuration of persistence of CAR T cells in the peripheral blood","definition_or_measurement_approach":"Measured as duration of detectable CAR T cells in peripheral blood over time (no further assay details provided)."}
• {"endpoint_text":"- •\tDuration of B cell depletion in the peripheral blood","definition_or_measurement_approach":"Measured as duration of B cell depletion in peripheral blood (no further assay details provided)."}
• {"endpoint_text":"- •\tLevels of respective serum autoantibodies at week 24 including incidence of seroconversion -\tSLE: antinuclear antibodies (ANA), anti-double-stranded (ds)DNA, anti-nucleosomes, anti-Sm, anti-cardiolipin IgG, C3 C4","definition_or_measurement_approach":"Serum autoantibody levels at week 24 and incidence of seroconversion for specified antibodies in SLE."}
• {"endpoint_text":"- •\tLevels of respective serum autoantibodies at week 24 including incidence of seroconversion -\tSSc: ANA, anti-SCL70, anti-RNA polymerase III, anti-topoisomerase","definition_or_measurement_approach":"Serum autoantibody levels at week 24 and incidence of seroconversion for specified antibodies in SSc."}
• {"endpoint_text":"- •\tLevels of respective serum autoantibodies at week 24 including incidence of seroconversion -\tIIM: ANA, anti-Mi2, anti-Tif1, anti-MDA5, anti-Jo1, anti-NXP2","definition_or_measurement_approach":"Serum autoantibody levels at week 24 and incidence of seroconversion for specified antibodies in IIM."}
• {"endpoint_text":"- •\tExpansion of CAR T cells in the patient over time","definition_or_measurement_approach":"Assessment of CAR T cell expansion over time in patients (no further assay details)."}
• {"endpoint_text":"- •\tSuccess of the manufacturing process by Good Manufacturing Practice (GMP) certification of the product","definition_or_measurement_approach":"Measured by GMP certification status/success of manufacturing process (no further detail)."}
• {"endpoint_text":"- •\tGeneral: -\tPatient’s Global Assessment (PtGA) of disease activity (visual analogue scale [VAS] 0-100mm)","definition_or_measurement_approach":"Patient-reported PtGA using VAS 0-100mm."}
• {"endpoint_text":"- •\tGeneral: -\tPhysician’s Global Assessment (PhGA) of disease activity (VAS 0-100mm)","definition_or_measurement_approach":"Physician-reported PhGA using VAS 0-100mm."}
• {"endpoint_text":"- •\tGeneral: -\tHealth Assessment Questionnaire – Disease Index (HAQ-DI)","definition_or_measurement_approach":"HAQ-DI assessment (standard questionnaire)."}
• {"endpoint_text":"- •\tGeneral: -\tFunctional Assessment of Chronic Illness Therapy - Fatigue (FACIT Fatigue)","definition_or_measurement_approach":"FACIT-Fatigue questionnaire assessment."}
• {"endpoint_text":"- •\tGeneral: -\tCore Quality of Life (EORTC QLQ-C30)","definition_or_measurement_approach":"EORTC QLQ-C30 quality of life questionnaire."}
• {"endpoint_text":"- •\tGeneral: -\tExtension phase only: incidence and severity of Adverse Events after reduced LD","definition_or_measurement_approach":"Incidence and severity of AEs in extension phase after reduced lymphodepletion (LD); measured by AE reporting (no further detail)."}
• {"endpoint_text":"- •\tSLE: -\tBritish Isles Lupus Assessment Group (BILAG) index","definition_or_measurement_approach":"BILAG index measurement for SLE disease activity."}
• {"endpoint_text":"- •\tSLE: -\tSystemic Lupus Erythematosus Disease Activity Index (SLEDAI)","definition_or_measurement_approach":"SLEDAI score for SLE disease activity."}
• {"endpoint_text":"- •\tSSc: -\tmodified Rodnan Skin Score (mRSS)","definition_or_measurement_approach":"mRSS for SSc skin involvement."}
• {"endpoint_text":"- •\tIIM: -\tPhysician’s global assessment (PhGA) of extramuscular activity","definition_or_measurement_approach":"Physician's global assessment of extramuscular activity in IIM."}
• {"endpoint_text":"- •\tIIM: -\tManual Muscle Testing (MMT)","definition_or_measurement_approach":"MMT assessment for muscle strength in IIM."}

Germany

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

08-07-2025

Processing Time Days

344

Number Of Sites

1

Number Of Participants

33

Primary sponsor

Full Name

Miltenyi Biomedicine GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"EvidentlQ Germany GmbH","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"International Drug Development Institute","duties_or_roles":"code 10; code 6","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Erlangen AöR","duties_or_roles":"code 14; code 15 - Investigational Medicinal Product Manufacturer","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Erlangen AöR","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Erlangen AöR","duties_or_roles":"code 1; code 8","organisation_type":"Hospital/Clinic/Other health care facility"}