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

An Open-label, Multi-center, Single-arm Phase 1/2 Study to Assess Tolerability, Safety and Efficacy of CRC01 in Participants With Severe, Refractory Autoimmune Diseases: Systemic Lupus Erythematosus

The purpose of this clinical trial is to evaluate the safety and efficacy of CRC01, an investigational autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, in people with lupus nephritis (LN), a serious kidney complication of systemic lupus erythematosus (SLE).

The main objectives of the study are:

1. To determine whether CRC01 infusion can improve kidney outcomes and reduce disease activity in participants with lupus nephritis.
2. To assess the safety profile, including potential risks such as cytokine release syndrome (CRS) and neurotoxicity.

Study Design This is a single-arm, open-label, multi-center, Phase 1/2 study. All enrolled participants will receive CRC01 after screening and baseline assessments.

Study Procedures

Participants will:

• Undergo eligibility screening, including blood tests, urine tests, and disease activity assessments.
• Provide autologous T lymphocytes through a procedure called leukapheresis.
• Receive a lymphodepleting pre-conditioning regimen (short course of chemotherapy).
• Receive a single intravenous infusion of CRC01 cells.
• Be hospitalized for close monitoring to detect and manage early adverse events such as CRS or neurotoxicity.
• Return for scheduled follow-up assessments through Week 52 (12 months) post-infusion to evaluate safety and treatment response.

Key Outcomes

Researchers will measure:

• Changes in proteinuria and kidney function.
• Changes in disease activity scores.
• Incidence and severity of adverse events.

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.