Phase IIa Trial of Anti-CD19 CAR T-Cells in Systemic Sclerosis Resistant to Immunosuppressive Therapy

NCT07493395 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RECHMPL24_0438
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Scleroderma, Systemic

Keywords

Systemic Sclerosis; Anti-CD19 CAR T-cells; Autologous CAR T-cell therapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (122)

• Change in European Scleroderma Trial And Research (EUSTAR) activity index

  From 3 months to 1 month before CAR-T cell infusion

• Change in European Scleroderma Trial And Research (EUSTAR) activity index

  1 month before CAR-T cell infusion

• Change in European Scleroderma Trial And Research (EUSTAR) activity index

  Day 0 (CAR-T cell infusion)

• Change in European Scleroderma Trial And Research (EUSTAR) activity index

  Day 28 after CAR-T cell infusion

• Change in European Scleroderma Trial And Research (EUSTAR) activity index

  3 Months

Study Arms (1)

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

Biological: CD19 CAR T Arm

Interventions

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.

CD19 CAR T Arm

Eligibility Criteria

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

You may qualify if:

• 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 :
• mRSS \>15 with at least one organ involvement (lung: FVC \<80%, renal involvement, cardiac involvement, Creatinine \< 1.5 mg/dl within 6 months).
• mRSS \<15 and lung fibrosis progression (FVC -10% DLCO -15% within 6 months)
• 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 :
• serum Creatinine clearance \> 40ml/mi
• adequate bone marrow function (Hemoglobin ≥9g/dL ; PMN ≥ 1 G/L ; Platelets ≥ 100 G/L)
• Alanine aminotransferase (ALT) ≤ 3 x ULN and total bilirubin \< 2.0 mg/dL (34 μmol/L) (or \< 3.0 mg/dL \[51 μmol/L\] for subjects with Gilbert's syndrome)
• Adequate respiratory function: no dyspnea or grade I dyspnea (Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0) and oxygen saturation \>/= 92% on room air
• Highly effective contraception methods

You may not qualify if:

• Craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia or cerebrovascular hemorrhagic diseases
• ECG showing prolonged QT interval or history of severe heart diseases or FEVG \< 40%
• Lung and / or heart severe dysfunction defined by CVF\<50% and/or DLCO \<40%
• Pulmonary arterial hypertension defined by catheterism (mean AP \> 25mmHg at rest or \> 30mmHg after exercise, PAOP \< 15mmHG)
• Clinically significant active, opportunistic, chronic or recurrent infection (including but not limited to: hepatitis B or C virus or HIV) or covid-19 \< 1 months including active or latent tuberculosis (TB) infection
• Contra indication for autologous hematopoietic stem cell transplantation (AHSCT ) or relapsing at least one year after AHSCT
• Active hematological or solid neoplasm
• Methylprednisolone or prednisone (maximum dose 20 mg) instead of immunosuppressive agents
• T cell targeting drugs (e.g. mycophenolate mofetil, azathioprine, calcineurin inhibitors) within 6 weeks prior to leukapheresis
• Previous adoptive T cell therapy or any gene therapy including CAR T cell therapy
• Live vaccines within 6 weeks prior to leukapheresis
• Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative chemotherapy or rescue medication/salvage therapies for treatment related toxicities
• patients without social security coverage;
• patients under guardianship;
• Male or female patients seeking to conceive a child

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (4)

CHRU Lille

Lille, France

Location

Montpellier University Hospital

Montpellier, France

Location

APHP Necker

Paris, France

Location

Chu Rouen

Rouen, France

Location

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Christian Jorgensen, PUPH

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte KAAN

CONTACT

04 67 33 48 53; c-kaan@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 25, 2026
• Study Start: April 1, 2026
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)