NCT07364396尚未招募1 期
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
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 39
- 主要终点
- Phase 1 Study: To evaluate the tolerability of CRC01 in patients with severe refractory autoimmune disease (systemic lupus erythematosus), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)
研究概览
简要总结
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:
- To determine whether CRC01 infusion can improve kidney outcomes and reduce disease activity in participants with lupus nephritis.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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.
研究组 & 干预措施
CRC01
Experimental
Participants with lupus nephritis will receive a single intravenous infusion of CRC01 (autologous anti-CD19 CAR-T cells) following lymphodepleting pre-conditioning chemotherapy.
干预措施: CRC01 (Biological)
结局指标
主要结局
Phase 1 Study: To evaluate the tolerability of CRC01 in patients with severe refractory autoimmune disease (systemic lupus erythematosus), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)
时间窗: 28 day
Safety and tolerability will be assessed by: 1\. Number of participants with dose-limiting toxicities (DLTs) within 28 days after CRC01 infusion, as assessed by CTCAE v5.0 and ASTCT consensus criteria.
Phase 2 Study: To evaluate the efficacy of CRC01 by assessing Complete Renal Response (CRR)
时间窗: 24 weeks
Complete Renal Response (CRR): Defined as meeting all of the following criteria: 1\. 24-hour urine protein ≤0.5 g, or urine protein-to-creatinine ratio (UPCR) ≤0.5. If a 24-hour urine collection is available and meets adequacy criteria, 24-hour urine protein assessment takes precedence. If the 24-hour urine collection is inadequate or not performed, UPCR will be used for evaluation.
次要结局
- Complete Renal Response (CRR) or Partial Renal Response (PRR) at each assessment Visit(Up to Week 52)
- Change From Baseline in Urine Protein-to-Creatinine Ratio (UPCR)(up to Week 52)
- Change From Baseline in Serum Creatinine(up to Week 52)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(up to Week 52)
- Change from baseline in UPCR, serum creatinine, urine protein, and eGFR(up to Week 52)
- Time to achieve UPCR ≤0.5(Up to Week 52)
- Change from baseline in SLEDAI-2K scores(Weeks 12, 24, and 52)
- Change From Baseline in Physician's Global Assessment at Week 12(Week 12)
- Change From Baseline in Physician's Global Assessment at Week 24(Week 24)
- Change From Baseline in Physician's Global Assessment at Week 52(Week 52)
- Achieving LLDAS at each assessment Visit(Weeks 12, 24, and 52)
- Change from baseline in SF-36 scores(Weeks 12, 24, and 52)
- Change from screening in immunology parameters(up to Week 52)
研究者
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