CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease

NCT06347718 | Recruiting Phase 1 DMC

• 3 other identifiers: CASTLE2022-001366-35DRKS00032279
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus; Systemic Sclerosis; Dermatomyositis; Polymyositis

Outcome Measures

Primary Outcomes (1)

• To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM).

  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.

  up to d 28

Secondary Outcomes (15)

• Clinical efficacy SSc

  at week 24

• Clinical efficacy SLE

  at week 24

• Clinical efficacy DM

  at week 24

• Cellular response

  up to week 24

• Serological response

  up to week 24

Study Arms (1)

Active dose

OTHER

A prospective, open-label, non-randomized, single-dose interventional basket study. Single 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. No control intervention (e.g. another immunosuppressive therapy). Concomitant measures: Leukapheresis and lymphodepleting therapy for conditioning.

Drug: anti-CD19 CAR T cell therapy

Interventions

anti-CD19 CAR T cell therapy DRUG

Single-dose

Active dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General:
• Subjects must understand and voluntarily sign an informed consent form including written 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.
• SLE specific:
• Fulfilling the 2019 ACR/EULAR classification criteria of SLE,
• 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),
• 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 specific:
• Fulfilling the 2013 ACR/EULAR classification criteria of SSc),

You may not qualify if:

• 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 the subject 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,
• 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,

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

Study Sites (1)

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

RECRUITING

Related Publications (1)

• Muller F, Hagen M, Wirsching A, Kharboutli S, Aigner M, Volkl S, Kretschmann S, Tascilar K, Taubmann J, Bucci L, Raimondo MG, Bergmann C, Rothe T, Corte G, Tur C, Munoz L, Boltz S, Schuster L, Hartmann F, Garantziotis P, Sporl S, Vasova I, Gerbitz A, Spriewald B, Kiener H, Giannarelli D, Locatelli F, D'Agostino MA, Hanssens L, Miltenyi S, Bozec A, Grieshaber-Bouyer R, Mackensen A, Schett G. CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial. Nat Med. 2026 Jan 7. doi: 10.1038/s41591-025-04185-6. Online ahead of print.

  PMID: 41501497 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Scleroderma, Systemic; Dermatomyositis; Polymyositis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Georg Schett, Prof. Dr. med. univ.

  Universitätsklinikum Erlangen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georg Schett, Prof. Dr. med. univ.

CONTACT

+49 9131 85 32093; georg.schett@uk-erlangen.de

Daniela Bohr, Dr.med

CONTACT

+49 9131 85 32093; daniela.bohr@uk-erlangen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: Evaluating the safety of CAR-T-Cells in systemic autoimmune diseases with 8 patients Phase 2: Evaluating the efficiency of CAR-T-Cells in systemic autoimmune diseases with 16 patients

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: April 4, 2024
• Study Start: July 17, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)