Lupus Nephritis
Conditions
Brief summary
This investigator-initiated trial aims to assess the efficacy and safety of combination therapy using universal CAR-T cells targeting BCMA and CD19 in refractory lupus nephritis.
Detailed description
This study is a non-randomized, open-label, single-arm clinical trial designed to assess the efficacy and safety of combination therapy for refractory lupus nephritis using universal CAR-T cells targeting BCMA and CD19.
Interventions
BIOLOGICALBCMA CART + CD19 CART
BCMA CART + CD19 CART
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-65 years; both genders eligible. * Subjects diagnosed with lupus nephritis. * Previous treatment outcomes were unsatisfactory. * Diagnosis of active nephritis type III or IV with or without type V according to 2018 International Society of Nephrology and Society of Renal Pathology (ISN/RPS) criteria. * NIH Activity Index \> 2 and elevated chronicity index. * Urine protein: creatinine ratio (UPCR) ≥ 1.0 g/g, or 24-hour urine protein ≥ 1.0 g, with or without active urine sediment with red blood cell casts. * Receiving hormones with or without antimalarials. * SLEDAI-2K score ≥ 6. * Antinuclear antibody positive, and/or anti-ds-DNA antibody positive, and/or anti-Smith antibody positive. * Positive expression of CD19 on B cells in peripheral blood. * Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication. * Provides written informed consent.
Exclusion criteria
* History of solid organ transplantation. * Malignant tumor within the last two years. * Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), with peripheral blood Hepatitis B virus (HBV) DNA detected as positive; positive for Hepatitis C virus antibodies, with peripheral blood Hepatitis C virus RNA detected as positive; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis. * Primary immunodeficiency (congenital or acquired). * Severe cardiac disease. * History of psychiatric disorders or history of psychotropic drug abuse, with no history of withdrawal. * Allergic constitution or a history of severe allergies. * Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs | Within 6 months after BCMA CART and CD19 CART infusion | The total number, incidence, and severity of AE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR (CR and PR) | At 6 months after BCMA CART and CD19 CART infusion | Complete response (CR) was defined as serum creatinine ≤ 1.2 mg/dl or ≤ 125% of baseline value, and urine protein/creatinine ratio \< 0.5 or 24-hour urine protein quantification \< 0.5 g, and prednisone dose reduction to ≤ 10 mg/d (or equivalent dose). Partial response (PR) was defined as if both serum creatinine and urine protein/creatinine ratio (or 24-hour urine protein quantification) were abnormal before treatment, both items improved by \> 30% after treatment, without other indicators of deterioration; if only urine protein/creatinine ratio (or 24-hour urine protein quantification) was abnormal before treatment, the improvement was \> 50% after treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PK/PD | Within 3 months after BCMA CART and CD19 CART infusion | Changes and duration of CAR gene copy number and CAR-T cell number in peripheral blood after BCMA CART and CD19 CART infusion |
Contacts
Primary ContactDandan Wang, PhD
Outcome results
None listed