A Phase IIa Trial Evaluating the Efficacy of anti-CD19 Chimeric Antigen Receptor Engineered T-Cells in Patients With Systemic Sclerosis (SSc) Resistant to Immunosuppressive Drugs. SCLEROCAR

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-11-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Programme Hospitalier de Recherche Clinique National · Institut Hospitalo Universitaire Immun4cure · Laboratoire Miltenyi

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the clinical efficacy of the CAR T ANTI-CD19 cell therapy on skin fibrosis assessed by mRSS score month 6 after CAR T ANTI-CD19 cell administration in patients with systemic sclerosis resistant to immunosuppressive drugs.

Secondary objectives 3

1. To evaluate the clinical efficacy of the CAR T ANTI-CD19 cell therapy on disease activity (EUSTAR index and mRSS), pulmonary and cardiac function month 3, 6 and 12;
2. To evaluate the safety profile of the CAR T ANTI-CD19 cell therapy at the target dose of 1 × 106 cells/kg (0.75 to 1.25 × 106) during the 12-months of post-injection follow up
3. To evaluate the pharmacokinetic (PK) profile of the transferred CAR T cells in scleroderma.

Conditions and MedDRA coding

Patients will be included with a stable but active disease (as defined Diagnosis of systemic sclerosis according to ACR/EULAR classification by EUSTAR ≥2.5) or to patients with a worsening disease despite low dose steroids and at least 2 immunosuppressive treatment including DMARDs (methotrexate, azathioprine, mycophenolate mofetil) and/or a biological DMARD (rituximab or tocilizumab) for at least 6 months.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of systemic sclerosis according to ACR/EULAR classification
2. 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.
3. Age: ≥18 ≤65 years old
4. Adequate organ functions assessed within 4 weeks of inclusion:
5. Adequate venous access for apheresis
6. Leucapheresis : a wash-out period of 6 weeks for conventional immunosuppressants (i.e. methotrexate, mycophenolate mofetil)
7. Leucapheresis : at least 3 months after biotherapy (i.e. tocilizumab, 6 months for rituximab),

Exclusion criteria 11

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 10

1. Change in the EUSTAR activity index (EUSTAR AI)
2. Change in mRSS
3. Change in the lung capacity FVC (forced vital capacity) and DLCO
4. Extension of fibrosis through pulmonary TDM
5. Change in cardiac ejection fraction and global longitudinal strain
6. Change in scleroderma-adapted Health Assessment Questionnaire (SHAQ) score.
7. Change in Health Assessment Questionnaire Disability Index HAQ-DI score
8. Incidence rate of adverse events
9. Incidence rate of AE of special interest (AESI)
10. Pharmacokinetic parameters linked to CART quantification (Tmax, Cmax, AUC), as well as the subpopulations of B and T immune cells,

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

39 Avenue Charles Flahault

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Pr Christian Jorgensen

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Pr Christian Jorgensen

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 24 files

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

Application history

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