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The goal of this clinical trial is to evaluate whether anti-CD19 CAR T-cell therapy can improve disease activity in adults with severe, treatment-resistant systemic sclerosis (SSc). The study will also assess the safety of this therapy and how CAR T-cells behave in the body.
The main questions are:
Does CAR T-cell therapy reduce skin thickening and other signs of SSc? What side effects occur after receiving CAR T-cells? How do CAR T-cells expand, persist, and affect B-cells and autoantibodies?
Participants will:
Undergo leukapheresis Receive short lymphodepleting chemotherapy Receive one infusion of anti-CD19 CAR T-cells Stay in the hospital for about 10 days Attend follow-up visits for 24 months with clinical exams, blood tests, and organ-function assessments
Optional skin or lymph-node biopsies may be performed in participants who consent to these procedures.
This study aims to provide early evidence on whether CAR T-cell therapy could become a promising treatment option for systemic sclerosis.
Systemic sclerosis (SSc) is a rare and severe autoimmune disease characterized by fibrosis of the skin and multiple organs, vasculopathy, and immune dysregulation. Many patients continue to experience active and progressive disease despite conventional immunosuppressive treatments, including disease modifying antirheumatic drugs (DMARDs) and biologics. Therapeutic options remain limited, and there is a significant unmet medical need for innovative approaches targeting the underlying mechanisms of the disease.
Recent preliminary experience from studies conducted in autoimmune diseases-such as lupus, myositis, and systemic sclerosis-suggests that autologous anti CD19 CAR T cell therapy may help reduce disease activity. Reported observations include transient B cell depletion, decreases in autoantibody levels, and improvements in joint, pulmonary, and cardiac manifestations. These early results support further evaluation of CAR T cell therapy in systemic sclerosis in a structured clinical trial setting.
This Phase IIa, multicenter, single-arm study is designed to evaluate the feasibility and safety of autologous anti-CD19 CAR-T cell therapy in adults with active systemic sclerosis who are resistant to immunosuppressive treatments. The study also aims to generate early clinical and biological data to assess the potential value of this therapeutic strategy in this population.
Eligible participants will undergo leukapheresis for T-cell collection. Following standard manufacturing of autologous anti-CD19 CAR-T cells in a GMP (Good Manufacturing Practice)-certified facility, participants will receive a short course of lymphodepleting chemotherapy, followed by a single intravenous infusion of CAR-T cells. They will remain hospitalized for intensive monitoring during the early post-infusion period, in accordance with established procedures for CAR-T cell therapies. Participants with known hypersensitivity to drugs required for treatment-related toxicity are excluded, as specified in the protocol.
After discharge from the hospital, participants will have follow-up visits for up to 24 months. These visits will include clinical and biological assessments as well as appropriate imaging tests to monitor disease activity, treatment safety, and overall health status. Biological samples will also be collected at specific times for centralized analysis.
The study incorporates exploratory immunological and translational research components. These may include monitoring circulating CAR T cells, characterizing immune cell subsets, and evaluating selected biomarkers. Optional skin and lymph node biopsies may be performed in consenting participants to analyze immune cell phenotypes and tissue level changes associated with treatment. Additional exploratory analyses may assess the spatial organization and distribution of immune cells within tissue samples, as described in the study protocol.
Overall, the study aims to provide early data on the use of anti CD19 CAR T cell therapy in systemic sclerosis, including feasibility, safety, and biological signals of activity. The results are expected to contribute to the development of innovative cell based therapeutic strategies for this severe autoimmune disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CD19 CAR T Arm | Experimental | Participants assigned to this arm will undergo leukapheresis and receive a lymphodepleting chemotherapy regimen, followed by a single intravenous infusion of autologous anti-CD19 CAR T-cells on Day 0. All participants enrolled in the study are included in this single experimental arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD19 CAR T Arm | Biological | Autologous anti-CD19 CAR-T cells are generated from the participant's leukapheresis product in a Good Manufacturing Practice (GMP)-certified facility using a lentiviral vector. Prior to infusion, participants will receive a short course of lymphodepleting chemotherapy. A single intravenous infusion of autologous anti-CD19 CAR-T cells will be administered on Day 0 at a target dose of 1 × 10⁶ CAR-T cells/kg. Participants will then be monitored in the hospital in accordance with standard post-CAR-T cell infusion procedures. |
| Measure | Description | Time Frame |
|---|---|---|
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease |
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Pre-Inclusion criteria:
Diagnosis of systemic sclerosis according to ACR/EULAR 2013 classification (15).we include in the critera the fulfilling of 2013 EULAR/ACR criteria and specify disease duration (less than 2 years), score/clinical evidence for active disease :
Severe and resistant to low dose steroids and at least 2 immunosuppressive treatment including csDMARDs (methotrexate, azathioprine, mycophenolate mofetil) and at least one bDMARDs (Tocilizumab)
Early onset (less than 2 years).
Severity & progression of disease be defined by :
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.
Estimated survival time > 24 weeks
Age: ≥18 ≤64 years old voluntary to participate in the study and sign the informed consent
Adequate organ functions assessed :
Highly effective contraception methods
Inclusion criteria:
Adequate organ functions assessed:
Adequate venous access for apheresis
Leucapheresis : a wash-out period of 6 weeks for conventional immunosuppressants (i.e. methotrexate, mycophenolate mofetil)
Leucapheresis : at least 12 weeks after biotherapy (i.e. tocilizumab, 6 months for rituximab),
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Charlotte KAAN | Contact | 04 67 33 48 53 | 33 | c-kaan@chu-montpellier.fr |
| Name | Affiliation | Role |
|---|---|---|
| Christian Jorgensen, PUPH | University Hospital, Montpellier | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU Lille | Not yet recruiting | Lille | France |
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| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
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A phase 2a, multicenter, open-label, single-arm study to investigate the efficacy of anti-CD19 CAR T-cell therapy in patients with systemic sclerosis who are resistant to immunosuppressive therapy
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| From 3 months to 1 month before CAR-T cell infusion |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | 1 month before CAR-T cell infusion |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | Day 0 (CAR-T cell infusion) |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | Day 28 after CAR-T cell infusion |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | 3 Months |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | 6 Months |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | 12 Months |
| Change in European Scleroderma Trial And Research (EUSTAR) activity index | Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease | 24 Months |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | From 3 months to 1 month before CAR-T infusion |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 1 month before CAR-T infusion |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | Day 0 (CAR-T infusion) |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | Day 28 after infusion |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 2 Months |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 3 Months |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 6 Months |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 12 months |
| modified Rodnan skin score (mRSS) | Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis) | 24 months |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | From 3 months to 1 month before CAR-T infusion |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 1 month before CAR-T infusion |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | Day 0 (CAR-T infusion) |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | Day 28 after infusion |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 2 Months |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 3 Months |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 6 Months |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 12 Months |
| Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) | Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score | 24 Months |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | From 3 months to 1 month before CAR-T infusion |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | 1 month before CAR-T infusion |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | 3 Months |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | 6 Months |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | 12 Months |
| Change in the lung capacity FVC (forced vital capacity) | To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time | 24 Months |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | From 3 months to 1 month before CAR-T infusion |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | 1 month before CAR-T infusion |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | 3 Months |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | 6 Months |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | 12 Months |
| Change in DLCO (diffusing capacity of the lung for carbon monoxide) | The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab | 24 Months |
| Extent of fibrosis on pulmonary CT (Computed Tomography) | Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb) | From 3 months to 1 month before CAR-T infusion |
| Extent of fibrosis on pulmonary CT(Computed Tomography) | Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb) | 3 Months |
| Extent of fibrosis on pulmonary CT(Computed Tomography) | Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb) | 12 Months |
| Extent of fibrosis on pulmonary CT(Computed Tomography) | Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb) | 24 Months |
| Change in cardiac ejection fraction and global longitudinal strain | A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS). | From 3 months to 1 month before CAR-T infusion |
| Change in cardiac ejection fraction and global longitudinal strain | A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS). | 3 Months |
| Change in cardiac ejection fraction and global longitudinal strain | A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS). | 12 Months |
| Change in cardiac ejection fraction and global longitudinal strain | A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS). | 24 Months |
| Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal | A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension | From 3 months to 1 month before CAR-T infusion |
| Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal | A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension | 12 Months |
| Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal | A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension | 24 Months |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | Day 0 (CAR-T infusion) |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | Day 28 after CAR-T cell infusion |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | 3 Months |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | 6 Months |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | 12 Months |
| Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score | Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage | 24 Months |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | Day 0 (CAR-T cell infusion) |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | Day 28 after CAR-T cell infusion |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | 3 Months |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | 6 Months |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | 12 Months |
| Change in Health Assessment Questionnaire Disability Index HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage | 24 Months |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | Day 0 (CAR-T cell infusion) |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | Day 28 after CAR-T cell infusion |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | 3 Months |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | 6 Months |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | 12 Months |
| Change in Health Assessment Questionnaire Cochin Hand score | Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment. | 24 Months |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the SF36 self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | Day 0 (CAR-T cell infusion) |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | Day 28 after CAR-T cell infusion |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | 3 Months |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | 6 Months |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | 12 Months |
| Change in quality of life Questionnaire SF-36 | Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health | 24 Months |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | Day 0 (CAR-T cell infusion) |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | Day 28 after CAR-T cell infusion |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | 3 Months |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | 6 Months |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | 12 Months |
| Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score | to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point | 24 Months |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | From 3 months to 1 month before CAR-T cell infusion |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | 1 month before CAR-T cell infusion |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | Day 0 (CAR-T cell infusion) |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | Day 28 after CAR-T cell infusion |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | 3 Months |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | 6 Months |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | 12 Months |
| Change in Malnutrition Universal Screening Tool (MUST) score | We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake | 24 Months |
| Anti-antibody titers | Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration | From 3 months to 1 month before CAR-T cell infusion |
| Anti-antibody titers | Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration | Day 28 after CAR-T cell infusion |
| Anti-antibody titers | Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration | 6 Months |
| Anti-antibody titers | Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration | 12 Months |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 0 (CAR-T cell infusion) |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 4 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 7 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 10 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 14 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 21 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | Day 28 after CAR-T cell infusion |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | 3 Months |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | 6 Months |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | 12 Months |
| CAR T cell counts | Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion | 24 Months |
| Immunophenotyping of B, T, and NK cells subsets | Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion | Day -14 (14 days before CAR-T infusion) |
| Immunophenotyping of B, T, and NK cells subsets | Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion | Day 28 after CAR-T cell infusion |
| Immunophenotyping of B, T, and NK cells subsets | Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion | 3 Months |
| Immunophenotyping of B, T, and NK cells subsets | Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion | 6 Months |
| Immunophenotyping of B, T, and NK cells subsets | Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion | 12 Months |
| B-cell receptor (BCR) repertoire analysis | BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration | Day -14 (14 days before CAR-T infusion) |
| B-cell receptor (BCR) repertoire analysis | BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration | 6 Months |
| B-cell receptor (BCR) repertoire analysis | BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration | 12 Months |
| B-cell receptor (BCR) repertoire analysis | BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration | 24 Months |
| Skin biopsies for single-cell phenotyping | Skin biopsies (for patients who have given their consent) performed at baseline for single-cell phenotyping analyses. | From 3 months to 1 month before CAR-T infusion |
| Skin biopsies for single-cell phenotyping | Skin biopsies (for patients who have given their consent) performed at M3 for single-cell phenotyping analyses. | 3 Months |
| lymph node biopsies for single-cell phenotyping | lymph node biopsies (for patients who have given their consent) performed at Month 3 for single-cell phenotyping analyses. | 3 Months |
| Incidence rate of adverse events | Incidence rate of adverse events graded according to the Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and classified following the American Society of Clinical Oncology (ASCO) guidelines | Day -14 to 24 months |
| Incidence of Cytokine Release Syndrome (CRS) | Incidence and severity of Cytokine Release Syndrome (CRS), graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system. | Day -14 to 24 months |
| Incidence of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) | Incidence and severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system | Day -14 to 24 months |
| Incidence of Cytopenias | Incidence and severity of cytopenias, graded according to the consensus grading system of the European Hematology Association (EHA) and the European Society for Blood and Marrow Transplantation (EBMT) consensus grading system | Day -14 to 24 months |
| Incidence of Infections | Incidence and severity of infections, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. | Day -14 to 24 months |
| Incidence of Cardiac Events | Incidence and severity of cardiac adverse events, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. | Day -14 to 24 months |
| Incidence of Acute Kidney Injury | Incidence and severity of acute kidney injury, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. | Day -14 to 24 months |
| Incidence of Scleroderma Renal Crisis | Incidence of clinically diagnosed scleroderma renal crisis | Day -14 to 24 months |
| Montpellier University Hospital | Recruiting | Montpellier | France |
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| APHP Necker | Not yet recruiting | Paris | France |
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| Chu Rouen | Not yet recruiting | Rouen | France |
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