CAR-T cells in SysTemic B celL mediated autoimmunE Disease

Phase 1

Recruiting

Conditions: M32
M33
M34
Systemic lupus erythematosus
Dermatopolymyositis
Systemic sclerosis

Registration Number: DRKS00032279

Lead Sponsor: Friedrich-Alexander-Universität Erlangen-Nürnberg, Medizinische Fakultät

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

General inclusion criteria
• Subjects must understand and voluntarily sign an informed consent form including writ-ten 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.

Disease-specific inclusion criteria
SLE subjects
• Fulfilling the 2019 ACR/EULAR classification criteria of SLE ([64]),
• 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) ([58]),
• 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 subjects
• Fulfilling the 2013 ACR/EULAR classification criteria of SSc ([14]),
• 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 ([56]),
• Insufficient response or intolerance/ contraindication to at least 2 of the following treat-ments: mycophenolate mofetil, azathioprine, nintedanib, methotrexate, rituximab. In-sufficient response is defined as having increased disease activity based on the defini-tion explained in the previous bullet point.

DM/PM subjects
• Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite DM or PM ([65]),
• 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 syn-thetases, 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 into

Exclusion Criteria

• 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 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 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 Investigator (e.g. family members).

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures