Anti-CD19 CAR T-Cell Therapy in Refractory Systemic Autoimmune Diseases

NCT06685042 | Recruiting Phase 1 DMC

• 2 other identifiers: 61922024-511293-74-01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The CATARSIS study explores the use of anti-CD19 CAR T-cell therapy as a novel approach for treating refractory systemic autoimmune diseases, specifically SLE, SSc, DM/PM, and AAV. These life-threatening conditions often resist current therapies, and B cells play a key role in their pathogenesis. The study employs CD19-CAR\_Lenti, an autologous CAR T-cell product targeting CD19-positive B cells, aiming to reduce inflammation and autoimmunity. This open-label, single-dose, phase I basket trial will assess the safety, feasibility, and preliminary efficacy of CAR T-cell therapy, focusing on adverse events, infection rates, and overall response at 24 weeks. Eight participants will be included.

Conditions

Lupus Erythematosus, Systemic; System; Sclerosis; ANCA Associated Vasculitis; Dermatomyositis; Polymyositis

Outcome Measures

Primary Outcomes (3)

• Number of subjects experiencing a CRS or an ICANS

  The first safety outcome variable will be measured as the number of subjects experiencing a Cytokine Release Syndrome (CRS) or an (Immune Effector Cell-associated Neurotoxicity Syndrome) ICANS within the first 4 weeks after ATMP administration in relation to the number of subjects enrolled in the study.

  4 weeks

• Incidence of infections, leukopenia and/or hypogammaglobulinemia

  The second safety outcome variable will be measured as the incidence of infections, leukopenia, and/or hypogammaglobulinemia during the entire study period in relation to the number of subjects enrolled in the study.

  24 weeks

• Overall Response Rate

  The efficacy outcome variable, Overall Response Rate (ORR), is defined as the ratio between the number of subjects experiencing a response at week 24 and the total number of enrolled subjects. A response to treatment will be considered at week 24 as: * SLE: Fulfillment of DORIS remission criteria of SLE. * SSc: No progression of interstitial lung disease with worsening of FVC (\>10%) or worsening of FVC (5-10%) plus an increase in respiratory symptoms or worsening of FVC (5-10%) plus progression of high-resolution computed tomography changes after 24 weeks. * DM/PM: 2016 ACR/EULAR Moderate or Major Response. * AAV: Birmingham vasculitis activity score (BVAS) of 0.

  24 weeks

Secondary Outcomes (3)

• Time of persistence of CAR T cells

  24 weeks

• Time of absence of B cells in the peripheral blood

  24 weeks

• Time to the disappearance of autoantibodies in the serum

  24 weeks

Other Outcomes (1)

• B cell receptor and T cell receptor repertoire

  24 weeks

Study Arms (1)

Anti-CD19 CAR T cell

EXPERIMENTAL

Single intravenous infusion of 1 x 106 /kg body weight CAR T cell ("CD19-CAR\_Lenti" )

Biological: CAR T cell

Interventions

CAR T cell BIOLOGICAL

The investigational medicinal product (IMP) "CD19-CAR\_Lenti" consists of autologous CD19 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells, derived from a leukapheresis product and processed by using the CliniMACS Prodigy® device (Miltenyi Biotec). CD19-CAR\_Lenti is a suspension of fresh CD4/CD8-enriched CD3+ T cells that have been genemodified with a self-inactivating (SIN) lentiviral vector expressing a CAR directed against human CD19. The SIN lentiviral vector is derived from clinically validated viral vectors described in the literature with a fully characterized sequence.

Anti-CD19 CAR T cell

Eligibility Criteria

• Age: 18 Years - 65 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 and \< 65 years at time of consent;
• 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 index \<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 (2 doses) against SARS-CoV-2 or SARS-CoV-2 within the last 6 months.
• SLE subjects
• a) Fulfilling the 2019 ACR/EULAR classification criteria of SLE; b) Presence of anti-dsDNA, anti-histone, anti-nucleosome or anti-Sm antibodies; c) 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); d) Insufficient response to glucocorticoids and at least 2 of the following treatments: hydroxychloroquine, mycophenolate mofetil, belimumab, methotrexate, rituximab.
• SSc subjects
• Fulfilling the 2013 ACR/EULAR classification criteria of SSc;
• Diffuse SSc with respective autoantibody profile;
• 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 ≥ 330 000/mm3), 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;
• Insufficient response to glucocorticoids and to at least 2 of the following treatments:
• mycophenolate mofetil, azathioprine, nintedanib, methotrexate, rituximab.

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 \< 8 g/dl, absolute CD3+ T cell count ≤100/µl;
• Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
• Relevant cardiovascular disease: recent history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, significant arrhythmia, congestive heart failure, or left ventricular ejection fraction \< 50%, as determined by echocardiography
• 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;
• Impaired renal function, i.e., eGFR \< 30 ml/min;
• Patients with evidence on thorax CT of advanced fibrotic interstitial lung disease and whose latest pulmonary function test showed a Forced Vital Capacity (FVC) \< 40% of predicted or a Diffusing Capacity for Carbon Monoxide (DLCO) \< 30% of predicted
• Any concomitant severe active infection, including HIV (even with negative viral load), active hepatitis B (either positive for Hepatitis B core antibody \[HBcAb\] or positive hepatitis B surface antigen \[HBsAg\] and NAT tests) and/or C (\<12 weeks between achievement of a sustained virological response to the specific treatment and apheresis) according to the American Association for the Study of Liver Diseases guidelines, SARS-CoV 2 (COVID 19), or active tuberculosis as defined by a positive Quantiferon TB-test. If the presence of latent tuberculosis is established, then treatment according to local guidelines must have been initiated before enrolment;
• Pregnant or lactating females;
• Known hypersensitivity to either any drug components or any auxiliary medicinal products scheduled during trial participation, including during lymphodepletion;
• Previous CAR T cell administration;
• A therapeutic schedule not compatible with the wash-out requirements for the leukapheresis procedure (section 5.8.1 of CSP) and the medications permitted during the study (section 7.11 of CSP);
• Concurrent treatment with other investigational agents or participation in other investigational trials.
• Treatment, as part of an investigational clinical trial, with an experimental product with a definite or potential effect on T or B-cells in the previous 2 years.
• Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis;

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, Lazio, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Scleroderma, Diffuse; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Dermatomyositis; Polymyositis

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Scleroderma, Systemic; Skin Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Maria Antonietta D'Agostino

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Antonietta D'Agostino

CONTACT

(+39)0630159650; mariaantonietta.dagostino@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: November 12, 2024
• Study Start: November 29, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 11, 2025

Record last verified: 2025-04

Locations

IT (1)