Phase I-IIa, national, multicenter, clinical trial to evaluate the safety and preliminary efficacy of CAR-T CD19 therapy in patients with refractory lupus nephritis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ICI24/00034 (Instituto de Salud Carlos III)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Evaluate the safety and tolerability of CD19 CAR-T cell therapy (TranspoCART19) in patients with refractory lupus nephritis during the early post-infusion period.

Conditions and MedDRA coding

Refractory Lupus Nephritis

Regulatory references

Scientific advice from competent authorities

Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Be able to give informed consent and to sign the informed consent form
2. For women of childbearing potential, a negative blood or urine pregnancy test is required at screening, at pre‑conditioning, and prior to infusion. They must also be willing to use a highly effective contraceptive method throughout their participation in the study. Sexually active male participants must use a condom from study entry until at least 12 months after administration of the investigational medicinal product and until CAR‑T cells are no longer detected in at least two consecutive qPCR tests. They must also refrain from donating semen during the same period. Condom use is required even for vasectomised men (as well as during sexual intercourse with a male partner or with a sterile female partner), since white blood cells are a normal component of semen and transmission of TranspoCART19‑transduced cells may occur
3. Patients aged ≥18 and ≤65 years with a diagnosis of systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.
4. At screening, a positive antinuclear antibody (ANA) test at a titre >1:80, or positivity for anti–double-stranded DNA (anti-dsDNA), or positivity for anti‑Smith (anti‑Sm) antibodies must be confirmed
5. Diagnosis of class III or IV proliferative lupus nephritis, with or without co‑existing class V, confirmed by a renal biopsy performed within the 6 months prior to signing the informed consent form, with evidence of active lupus according to the activity indices of the 2018 ISN/RPS (Revised International Society of Nephrology/Renal Pathology Society) classification. A recent biopsy is required prior to enrolling the patient in the study, accepting those performed within the 6 months before signing the informed consent form. A renal biopsy may be performed during the screening period if the previous biopsy exceeds the permitted timeframe. Patients may be included based on the evaluation of the locally performed biopsy; however, a subsequent central review will also be conducted by the study coordinating team in collaboration with an expert panel of nephropathologists. If a biopsy is not feasible due to safety reasons or lack of accessibility, active renal disease must be confirmed according to clinical and/or laboratory criteria, and the case must be discussed with the study coordinators, who will determine eligibility
6. Evidence of refractory or resistant lupus nephritis, according to the definition of the Glomerular Diseases Study Group of the Spanish Society of Nephrology (GLOSEN): ‘lack of response or clear worsening of proteinuria and/or renal function after at least three months of treatment with triple immunosuppressive therapy, according to the proposed regimens.’ In situations where triple therapy cannot be used, or where biological therapy cannot be administered, lupus nephritis will be considered refractory if there is a lack of clinical response or worsening of proteinuria and/or renal function after ≥6 months of adequate full‑dose immunosuppressive therapy combined with corticosteroids (unless corticosteroid intolerance is documented) and at least two of the following therapeutic options (each administered at full dose for a minimum of 3 months): cyclophosphamide, mycophenolic acid or its derivatives, tacrolimus, cyclosporine, voclosporin, azathioprine, methotrexate, rituximab, belimumab, obinutuzumab, or anifrolumab
7. Patients with an estimated glomerular filtration rate (eGFR) calculated using the CKD‑EPI 2009 creatinine equation ≥ 30 mL/min/1.73 m² (at least once during the screening period)
8. Urine protein-to-creatinine ratio (UPCR) >0.7 g/g (or urine albumin-to-creatinine ratio >0.5 g/g) at screening in a spot urine sample, or proteinuria >0.7 g/24 h (or 24-hour urine albumin ≥0.5 g/24 h) with evidence of active lupus nephritis on renal biopsy (according to the 2018 ISN/RPS classification)
9. All patients must be receiving treatment with an ACE inhibitor, an ARB, and/or a mineralocorticoid receptor antagonist (with or without SGLT2 inhibitors) for at least 3 months prior to screening (unless intolerance, contraindications, or low blood pressure that may induce adverse effects at the investigator’s discretion). The dose of the ACE inhibitor, ARB, and/or mineralocorticoid receptor antagonist (with or without SGLT2 inhibitors) must remain stable for at least 2 weeks prior to screening
10. Adequate venous access and no contraindication to performing a leukapheresis procedure
11. Participants must have received all vaccinations recommended according to the standard immunization schedule and those indicated for immunocompromised patients, including full vaccination/immunization against SARS‑CoV‑2, prior to or during the screening period
12. Be willing and able to read and fully understand the patient information sheet and to provide consent to participate, as well as to comply with the study procedures and follow‑up.

Exclusion criteria 21

1. Severe Organ Involvemen defined as any of the following findings during the screening period (each test may be repeated once if necessary): - Impaired cardiac function: Left ventricular ejection fraction (LVEF) <50% on conventional echocardiography performed during the screening period. In patients with reversible cardiac impairment due to SLE, LVEF during screening must be <40%. - Impaired hepatic function: ALT and AST >1.5 × ULN, total bilirubin (TB) >1.5 × ULN. Exceptions: Participants with previously diagnosed Gilbert’s syndrome or those with a positive Coombs test and laboratory evidence of SLE-induced hemolysis may be included if TB ≤3.0 × ULN and direct bilirubin ≤1.5 × ULN. INR >1.5. - Insufficient bone marrow reserve: Absolute neutrophil count ≤1000/μL, platelet count ≤75,000/μL, white blood cell count ≤3000/μL, lymphocytes ≤300/μL, hemoglobin ≤8 g/dL. - Reduced oxygen saturation: Oxygen saturation (SatO₂) <92% by pulse oximetry without oxygen therapy.
2. Diagnosis of another current or past malignancy. Patients may be eligible if they have been in complete remission for more than three years, or have a history of non-melanoma skin cancer or completely resected carcinoma in situ
3. History of major organ transplantation (e.g., heart, lung, kidney, liver) or transplantation of hematopoietic stem cells or bone marrow.
4. Anticipated need for scheduled major surgery within one year following administration of the investigational medication.
5. Receipt of live vaccines within 30 days prior to administration of the investigational medication.
6. Current drug or alcohol use or dependency that, in the investigator’s opinion, could interfere with compliance with study requirements.
7. Any other severe or uncontrolled medical or psychiatric condition (except the condition targeted by the study) that, in the investigator’s opinion, could compromise the participant’s ability to tolerate therapy with the investigational medication or the lymphodepletion regimen.
8. Pregnant or breastfeeding women.
9. Women of childbearing potential who are unwilling to use contraceptive methods throughout the study period.
10. Sexually active male participants who are unwilling to use condoms from inclusion in the study until at least 12 months after administration of the investigational medication and until no CAR-T cells are detected in at least two consecutive qPCR tests
11. Participation in another investigational drug trial within 90 days prior to signing the informed consent, or receipt of any experimental or non-commercialized treatment within the four weeks prior to signing the informed consent (or within the time equivalent to five half-lives of the drug, whichever is longer). 21. Inability or refusal to sign the informed consent form or comply with required follow-up during the study. Would you like me to compile all 21 exclusion criteria into one polished document-style section now? I can format it for regulatory clarity or integrate it into your protocol draft—whatever you need.
12. Planned initiation of renal replacement therapy during the study period, or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² (calculated using the CKD-EPI creatinine formula).
13. Inability or refusal to sign the informed consent form or comply with required follow-up during the study.
14. Evidence of any active infection requiring treatment during the screening period or prior to the lymphodepletion period
15. Positive screening result for HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), or evidence of active acute or chronic tuberculosis during the screening period.
16. Grade ≥ 2 thromboembolic event within the 4 weeks prior to or during the screening period.
17. Patients with a confirmed history of Progressive Multifocal Leukoencephalopathy (PML) or with neurological symptoms suggestive of PML prior to treatment
18. Requirement for systemic glucocorticoid administration at doses ≥ 30 mg/day of prednisone (or equivalent). Lower daily doses are permitted as long as they have remained stable for at least 2 weeks prior to the screening period.
19. Hypersensitivity to any of the active substances or excipients to be used during the study, including TraspoCART19 cells or, if applicable, the lymphodepletion regimen or any other treatment considered standard for this study.
20. Any concomitant systemic autoimmune disease requiring immunosuppressive treatment independent of SLE therapy and at risk of disease flare upon withdrawal of such treatment during the study periods
21. Prior treatment with anti‑CD19 CAR‑T therapy. Previous treatment with other anti‑CD19 alternatives is permitted, provided that the therapy has been discontinued at least 180 days before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the safety and tolerability of CD19 CAR‑T cell therapy (TranspoCART19) in patients with refractory lupus nephritis during the early post‑infusion period (Day 0–28; extended to Day +42 in cases of prolonged cytopenias)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

Sponsor organisation

Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

Address

Calle De Isaac Peral 42 Oficinas 2a Planta Oficina 1

City

Madrid

Postcode

28015

Country

Spain

Scientific contact point

Organisation

Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

Contact name

Alberto Ortiz

Public contact point

Organisation

Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

Contact name

Eva Cerezo Martín

Locations

1 EU/EEA country · 8 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 10 files

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

Application history

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