Anti-CD19 CAR T-Cell TherApy in Refractory Systemic Autoimmune DISeases - CATARSIS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

26 Nov 2024 → ongoing

Decision date (initial)

2024-08-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Italian Ministry of Health, Ricerca Finalizzata, Project code RF-2021-12375251, 31.03.2022

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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

Secondary objectives 1

1. To investigate the duration of B cell depletion after anti-CD19 CAR T cell administration. To investigate the duration of CAR T cell persistence after anti-CD19 CAR T cell ad- ministration. To investigate the changes in the levels of disease-associated serum autoantibodies.

Conditions and MedDRA coding

Refractory Systemic Autoimmune Diseases

Regulatory references

Plan to share IPD

No

IPD plan description

not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. General a) Subjects must understand and voluntarily sign an informed consent form including writ- ten consent for data protection; b) Adults aged ≥ 18 years and ≤ 80 years at time of consent; c) 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; d) 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; e) Must be able to adhere to the study visit schedule and other protocol requirements; f) Double vaccination (2 doses of vaccine)against SARS-CoV-2 or SARS-CoV-2 within the last 6 months.

Exclusion criteria 1

1. Subjects having any of the following criteria at screening will not be included in the study: - 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 was 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 presence of latent tuberculosis is established then treatment according to local guidelines must have been initiated prior to enrolment; - Pregnant or lactating females; - Known hypersensitivity to either any drug components or any auxiliary medicinal products scheduled during trial participation, including during lymphodepletion;; - Malignancy in the last 5 years before screening.The inclusion of patients with previously completely resected carcinoma in situ who have not required treatment other than surgery is allowed. - Previous CAR T cell administration; - A therapeutic schedule not compatible with the wash-out requirements for the leukapheresis procedure (section 5.8.1) and the medications permitted during the study (section 7.11); - 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 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; - 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - 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. - Incidence and severity of infections and leukopenia and/or hypogammaglobulinemia during the entire study period.

Secondary endpoints 1

1. a) Duration of B cell depletion in the peripheral blood: CD19+ B cells assessed by fluorescence- activated cell sorting (FACS) equal to 0 up to week 24 and long-term FU. b) Duration of persistence of CAR T cells in the peripheral blood: CAR+ CD3+ cells assessed by FACS > 0 up to week 24 and long-term FU. c) Changes in the levels of disease-associated serum autoantibodies at week 24 including incidence of seroconversion (anti-dsDNA < LLN; ANA <1.100; all others “negative”) o SLE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Professoressa Maria Antonietta D'Agostino

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Professoressa Maria Antonietta D'Agostino

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications