Autologous T-cells transduced with lentiviral vector expressing a chimeric antigen receptor directed against CD19 for Systemic sclerosis (scleroderma)

Inclusion criteria

• {"criterion_text":"- Diagnosis of systemic sclerosis according to ACR/EULAR classification"}
• {"criterion_text":"- Refractory corresponds to patients with active disease (as defined by EUSTAR ≥2.5) and to patients with a worsening disease despite 6 months of at least 2 immunosuppressive treatments including one DMARDs (methotrexate, azathioprine, mycophenolate mofetil), and one biological DMARD rituximab or tocilizumab."}
• {"criterion_text":"- Age: ≥18 ≤65 years old"}
• {"criterion_text":"- Adequate organ functions assessed within 4 weeks of inclusion:"}
• {"criterion_text":"- Adequate venous access for apheresis"}
• {"criterion_text":"- Leucapheresis : a wash-out period of 6 weeks for conventional immunosuppressants (i.e. methotrexate, mycophenolate mofetil)"}
• {"criterion_text":"- Leucapheresis : at least 3 months after biotherapy (i.e. tocilizumab, 6 months for rituximab),"}

Exclusion criteria

• {"criterion_text":"- Craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia or cerebrovascular hemorrhagic diseases"}
• {"criterion_text":"- pregnant or breastfeeding women"}
• {"criterion_text":"- patients with advanced cognitive disorders or any other cause preventing their informed consent"}
• {"criterion_text":"- ECG showing prolonged QT interval or history of severe heart diseases or FEVG < 40%"}
• {"criterion_text":"- Lung and / or heart severe dysfunction defined by CVF<50% and/or DLCO <40%"}
• {"criterion_text":"- Pulmonary arterial hypertension defined by catheterism (mean AP > 25mmHg at rest or > 30mmHg after exercise, PAPO < 15mmHG)"}
• {"criterion_text":"- Active infection (including but not limited to: hepatitis B or C virus or HIV) or covid-19 < 1 months"}
• {"criterion_text":"- Active hematological or solid neoplasm"}
• {"criterion_text":"- Methylprednisolone or prednisone (≤20 mg) instead of immunosuppressive agents"}
• {"criterion_text":"- Rituximab within 6 months to leukapheresis"}
• {"criterion_text":"- Live vaccines within 30 days prior to leukapheresis"}

Primary endpoints

• {"endpoint_text":"- Improvement of disease activity assessed from baseline to month 6 after CAR T ANTI-CD19 cell administration through change of at least 5 points in the modified Rodnan Skin Score (mRSS).","definition_or_measurement_approach":"Change of at least 5 points in the modified Rodnan Skin Score (mRSS) from baseline to month 6 after CAR T ANTI-CD19 cell administration."}

Secondary endpoints

• {"endpoint_text":"- Change in the EUSTAR activity index (EUSTAR AI)","definition_or_measurement_approach":"Change in EUSTAR activity index (EUSTAR AI) compared to baseline (timepoints referenced in objectives include month 3, 6 and 12)."}
• {"endpoint_text":"- Change in mRSS","definition_or_measurement_approach":"Change in modified Rodnan Skin Score (mRSS) compared to baseline."}
• {"endpoint_text":"- Change in the lung capacity FVC (forced vital capacity) and DLCO","definition_or_measurement_approach":"Change in forced vital capacity (FVC) and DLCO compared to baseline."}
• {"endpoint_text":"- Extension of fibrosis through pulmonary TDM","definition_or_measurement_approach":"Assessment of pulmonary fibrosis extent by thoracic imaging (pulmonary TDM)."}
• {"endpoint_text":"- Change in cardiac ejection fraction and global longitudinal strain","definition_or_measurement_approach":"Change in cardiac ejection fraction and global longitudinal strain compared to baseline."}
• {"endpoint_text":"- Change in scleroderma-adapted Health Assessment Questionnaire (SHAQ) score.","definition_or_measurement_approach":"Change in SHAQ score compared to baseline."}
• {"endpoint_text":"- Change in Health Assessment Questionnaire Disability Index HAQ-DI score","definition_or_measurement_approach":"Change in HAQ-DI score compared to baseline."}
• {"endpoint_text":"- Incidence rate of adverse events","definition_or_measurement_approach":"Incidence rate (number and proportion) of adverse events during the study period."}
• {"endpoint_text":"- Incidence rate of AE of special interest (AESI)","definition_or_measurement_approach":"Incidence rate (number and proportion) of adverse events of special interest."}
• {"endpoint_text":"- Pharmacokinetic parameters linked to CART quantification (Tmax, Cmax, AUC), as well as the subpopulations of B and T immune cells,","definition_or_measurement_approach":"Measurement of CAR T cell pharmacokinetic parameters (Tmax, Cmax, AUC) and quantification/characterisation of B and T immune cell subpopulations."}

France

Earliest CTIS Part Ii Submission Date

17-07-2025

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

264

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Montpellier

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Institut Hospitalo Universitaire Immun4cure","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Laboratoire Miltenyi","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Programme Hospitalier de Recherche Clinique National","duties_or_roles":"Source of monetary support","organisation_type":""}