Efficacy and Safety of CRC01 in Participants With Severe, Refractory Systemic Lupus Erythematosus

Inclusion criteria

• Age 19 years or older, voluntarily provides written informed consent.
• Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria.
• Positive antinuclear antibody (ANA) at screening (titer ≥1:80).
• Diagnosis of lupus nephritis Class III or IV (with or without concurrent Class V), confirmed by kidney biopsy within 1 year prior to screening based on ISN/RPS 2018 criteria.
• Inadequate response to, or intolerance of, at least two or more standard therapies for 6 months or longer (cyclophosphamide, mycophenolate mofetil, azathioprine, tacrolimus, rituximab, belimumab).
• Proteinuria at screening with urine protein-to-creatinine ratio (UPCR) >1.5.
• Adequate laboratory values at screening: Hemoglobin >8.0 g/dL; ANC >1,000/μL; Platelets ≥50,000/μL; Total bilirubin ≤2.0 × ULN; AST and ALT ≤3 × ULN; eGFR ≥30 mL/min/1.73 m².
• Hemodynamically stable, no pericardial effusion, and LVEF ≥50% by echocardiogram at screening.
• FEV1/FVC ≥70% at screening.
• Willing and able to comply with study visits, procedures, and requirements.
• Women of childbearing potential and men must agree to use effective contraception for at least 1 year after CRC01 infusion until PCR testing confirms clearance of CRC01.

Exclusion criteria

• Current or anticipated requirement for renal dialysis during the study.
• History of kidney transplantation or planned transplantation during the study.
• History of severe CNS lupus or currently active severe CNS lupus.
• Prior CAR-T cell therapy.
• History of malignancy except for: basal or squamous cell carcinoma of skin treated and disease-free ≥3 years; in-situ carcinoma of cervix or breast treated and disease-free ≥3 years; superficial bladder cancer treated and disease-free ≥3 years; completely resected primary malignancy in complete remission ≥5 years.
• Unstable angina and/or myocardial infarction within 1 year prior to screening.
• Congestive heart failure of NYHA Class III or IV within 1 year prior to screening.
• Thromboembolism, pulmonary embolism, or clinically significant bleeding diathesis within 6 months prior to screening.
• Hypoxemia, clinically significant pleural effusion, or abnormal ECG findings within 6 months prior to screening.
• Stroke (ischemic or hemorrhagic) within 6 months prior to screening.
• Positive HBsAg; positive anti-HCV (eligible if HCV RNA negative); known HIV infection; or active neurological autoimmune/inflammatory diseases (e.g., Guillain-Barré syndrome, ALS).
• Recurrent or symptomatic ventricular tachycardia, or atrial fibrillation with rapid ventricular response despite therapy within 3 months prior to screening.
• Severe or uncontrolled active infection requiring systemic therapy at screening.
• Rapidly progressive disease or otherwise unsuitable for study participation, per investigator judgment.
• Pregnant or breastfeeding women.
• Known hypersensitivity to investigational product components.
• Participation in another investigational study within 4 weeks prior to screening.
• Receipt of systemic corticosteroids at therapeutic doses within 7 days prior to leukapheresis (≤7.5 mg/day prednisone equivalent is permitted).
• Receipt of immunosuppressive agents within 7 days prior to leukapheresis.
• Receipt of antibody-based therapies (e.g., belimumab, rituximab, anifrolumab) within 4 weeks prior to leukapheresis.

Inclusion criteria

for CRC01 Infusion:

• No clinically significant worsening of organ function after screening.
• If any of the following adverse events related to lymphodepleting chemotherapy exceed Grade 1 or worsen compared with screening, CRC01 infusion must be delayed:

• Requirement for supplemental oxygen
• New arrhythmia symptoms or clinically significant changes in cardiac function compared with screening
• Hypotension requiring treatment
• Active infection within 72 hours prior to the planned CRC01 infusion

• If bacterial, viral, or fungal infection is documented, improvement of symptoms must be documented before infusion.
• Women of childbearing potential must have a negative urine pregnancy test prior to infusion.
• If CRC01 infusion is delayed for more than 2 weeks after lymphodepleting chemotherapy, administration may proceed only with approval from the sponsor's medical monitor.
• No receipt of therapeutic doses of systemic corticosteroids or immunosuppressive agents within 7 days prior to CRC01 infusion. (Prednisone ≤7.5 mg/day or equivalent is permitted.)
• No receipt of antibody-based therapies (e.g., belimumab, rituximab, anifrolumab) within 4 weeks prior to CRC01 infusion.