Phase I/IIa Multicenter Study of TranspoCART19 CD19 CAR‑T Cell Therapy in Patients with Refractory Lupus Nephritis: Safety and Preliminary Efficacy

Trial ID: 2025-522449-23-00
Protocol: CART-NEL
Sponsor: Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

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Diseases & Conditions

Lupus nephritis

Objectives

The primary objective is to assess the safety and tolerability of CD19 CAR‑T cell therapy (TranspoCART19) in patients with refractory lupus nephritis during the early post‑infusion period, providing essential data on adverse event profile and infusion‑related risks that are critical for advancing this novel cellular approach in a population with limited therapeutic options.

Participants

The sponsor did not provide the total number of participants. The trial enrolled adult individuals aged 18 to 65 years of both sexes who met the diagnostic criteria for systemic lupus erythematosus and exhibited refractory lupus nephritis confirmed by recent renal biopsy or clinical criteria. Eligible participants were required to have an estimated glomerular filtration rate of at least 30 mL/min/1.73 m², a urine protein‑to‑creatinine ratio exceeding 0.7 g/g (or equivalent 24‑hour proteinuria), and to be receiving a stable regimen of ACE inhibitor, ARB, and/or mineralocorticoid receptor antagonist for a minimum of three months. Additional selection factors included adequate venous access for leukapheresis, completion of recommended vaccinations—including SARS‑CoV‑2 immunization—and adherence to contraceptive requirements for women of childbearing potential and condom use for sexually active males. Participants were required to provide informed consent, demonstrate understanding of study procedures, and maintain compliance with follow‑up visits. The population thus comprised patients with active, treatment‑resistant lupus nephritis who were otherwise in a clinically stable condition permitting safe administration of CD19 CAR‑T cell therapy.

Plans and Procedures

The study is a Phase I‑IIa, national, multicenter, open‑label trial evaluating the safety and preliminary efficacy of a single intravenous infusion of the CD19‑directed CAR‑T cell product TranspoCART19 in adults with refractory lupus nephritis. After obtaining informed consent, participants undergo a screening visit to confirm eligibility, including renal biopsy review, laboratory assessments, and vaccination status. Eligible subjects receive a lymphodepleting conditioning regimen followed by the investigational infusion on Day 0. Serial safety assessments are performed on Days 7, 14, 21, 28, and, if cytopenias persist, on Day 42. Additional follow‑up visits occur at predefined intervals to monitor renal function, proteinuria, and immunologic parameters, culminating in an end‑of‑study visit that records final outcomes. Participant involvement therefore extends from the screening visit through at least Day 42 and the final assessment visit. Early termination may be instituted for significant adverse events, inability to complete required study procedures, or voluntary withdrawal of consent. The recruitment period is planned from May 2026 to December 2028, with each participant followed for the duration of the defined post‑infusion observation windows and the final study visit.

Treatment

The investigational product is TranspoCART19, a genetically modified autologous T‑cell product formulated as a cell suspension for infusion. The therapy is administered intravenously as a single infusion; the specific cell dose and volume are defined in the individual subject’s dosing plan and are prepared according to Good Manufacturing Practice specifications. The infusion is delivered over a pre‑specified period under continuous vital sign monitoring.

No additional investigational agents are administered in this study. Concomitant standard‑of‑care therapies for lupus nephritis may be continued at the discretion of the treating investigator, provided they do not interfere with the assessment of the investigational product.

Infusion procedures include pre‑medication with antipyretics and antihistamines as per protocol, real‑time observation for infusion‑related reactions, and post‑infusion monitoring for at least 24 hours. Compliance with the dosing schedule is ensured through documented confirmation of product receipt, infusion completion records, and electronic case report form entries. Safety assessments and laboratory evaluations are performed at defined intervals during the early post‑infusion period to evaluate tolerability.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Be able to give informed consent and to sign the informed consent form
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
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.
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
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
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
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)
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)
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
Adequate venous access and no contraindication to performing a leukapheresis procedure
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
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.

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Exclusion Criteria

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.
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
History of major organ transplantation (e.g., heart, lung, kidney, liver) or transplantation of hematopoietic stem cells or bone marrow.
Anticipated need for scheduled major surgery within one year following administration of the investigational medication.
Receipt of live vaccines within 30 days prior to administration of the investigational medication.
Current drug or alcohol use or dependency that, in the investigator’s opinion, could interfere with compliance with study requirements.
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.
Pregnant or breastfeeding women.
Women of childbearing potential who are unwilling to use contraceptive methods throughout the study period.
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
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.
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).
Inability or refusal to sign the informed consent form or comply with required follow-up during the study.
Evidence of any active infection requiring treatment during the screening period or prior to the lymphodepletion period
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.
Grade ≥ 2 thromboembolic event within the 4 weeks prior to or during the screening period.
Patients with a confirmed history of Progressive Multifocal Leukoencephalopathy (PML) or with neurological symptoms suggestive of PML prior to treatment
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.
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.
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
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