A Safety, Efficacy, and Pharmacokinetics Study of Anti-CD19 CAR-T Cell Therapy in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
This is an open, Phase I, investigator-initiated study (IIT) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of RD06-04 in patients with moderate or severe active SLE. This study will explore the safety of escalating doses of RD06-04 by presetting two dose levels (DL), with 3 to 6 patients enrolled in each dose level. After safety conclusions are reached in each group, the investigator can select the corresponding dose group to expand cases based on treatment response, but the total number of cases will not exceed 12. This study will enroll patients in a 3+3 design with two DLS: 1×105 CAR+T cells /kg for DL1 and 5×105 CAR+T cells /kg for DL2. Dose increment Refer to the 3+3 dose increment principle. Three subjects are expected to be enrolled in each dose group. 1. Dose increment should start from the minimum dose, and it is not possible to conduct an incremental study of 2 or more dose groups at the same time. 2. If 1 case of DLT occurs in each dose group, the dose level will be extended to 6 subjects. If 6 subjects at this dose level ≥2 subjects develop DLT, the dose level exceeds the MTD. The previous lower dose level will be extended to 6 subjects, and if 6 subjects have already been enrolled in the previous lower dose level, and only ≤1 of these 6 subjects develop DLT, this lower dose level will be considered MTD. 3. If DLT occurred in ≥2 subjects in the highest dose group, the researcher could select a dose between the high dose group and the medium dose group according to the specific situation and perform MTD evaluation. 4. If the dose increase to the highest dose group still does not reach DLT, researchers can explore the safety and efficacy of higher doses according to specific circumstances. Case expansion: After the completion of DLT evaluation in all dose groups, the investigators could select the corresponding dose group of extended cases according to the treatment response, but the total number of cases should not exceed 12 (extended cases were not evaluated by DLT).
• 1.The subjects voluntarily participated in the experiment and signed the informed consent.
• 2\. Age ≥18 years old and ≤70 years old, regardless of gender. 3. Diagnosis of SLE according to the European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria 2019 or the 2012 International Clinical Collaboration Group on Systemic Erythraeus (SLICC) criteria.
• 4\. Prior to screening, patients must have been treated with glucocorticoids combined with immunosuppressants and/or biologics for at least 2 months, and the dose is stable for \>2 weeks, and the disease is still active (i.e., previous treatment with glucocorticoids + immunosuppressants or glucocorticoids + immunosuppressants + biologics, and any of the above drugs are not eligible for single drug use). Oral corticosteroids must meet the following requirements: 1) Prednisone (or equivalent) ≥7.5mg/ day; 2) There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants and/or biologics.
• 5\. Screening is positive for antinuclear antibody (ANA), and/or anti-DS-DNA antibody, and/or anti-Smith antibody.
• 6\. The SLEDAI-2K score in the screening period was \>6, and the clinical SLEDAI-2K score was ≥4.
‣ Note: Clinical SLEDAI-2K is a score in the SLEDAI-2K score that does not include results attributable to any urine or laboratory tests (including immunological indicators) :
‣ 7\. The BILAG2004 score meets at least one of the following conditions:
‣ a) ≥1 organ system BILAG2004 Class A disease b) ≥2 organ systems BILAG2004 Class B disease 8. Physician General assessment (PGA) score ≥1.0 (0-3 on visual analogue scale VAS) during screening.
‣ 9\. Organ function and laboratory tests:
⁃ Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST≤3× upper normal limit (ULN), total bilirubin (TBIL) ≤2×ULN (except Gilbert syndrome).
⁃ Renal function: creatinine ≤1.5×ULN or creatinine clearance ≥40 ml/min.
⁃ Blood routine: neutrophil count ≥1×109/L, hemoglobin ≥60g/L, platelet count ≥20×109/L, lymphocyte count \>0.3×109/L.
⁃ Coagulation function: International standardized ratio (INR) ≤ 1.5×ULN, or prothrombin time (PT) ≤ 1.5×ULN.
⁃ Blood oxygen saturation (SpO2) at rest in indoor air ≥92%.
⁃ Echocardiography showed left ventricular ejection fraction (LVEF) ≥50%. 10. The serum or urine pregnancy test results of fertile female subjects at the time of screening were negative.
⁃ 11\. Fertile women must consent to the use of highly effective contraceptive methods for contraception from at least 28 days before the start of the infusion until 12 months after the RD06-04 reinfusion. Fertile men must consent to the use of an effective barrier method of contraception from the start of DTP until 12 months after RD06-04 reinfusion, and should not donate semen or sperm throughout the trial period.