Safety and Efficacy of PRG-2311 for Refractory Lupus Nephritis and IgG4-Related Disease
NCT Number: NCT06497361
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: EARLY_PHASE1
Conditions: Lupus Nephritis|IgG4-related Disease
Interventions: BIOLOGICAL: PRG-2311
Sponsor: Tongji Hospital
Collaborators: Shenzhen Pregene Biopharma Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07
Completion Date: 2028-07
Locations: Tongji Hospital, Wuhan, Hubei, 430030, China

Summary:
A Clinical Study on the Safety and Effectiveness of CD19/BCMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Lupus Nephritis and IgG4-Related Disease.

Primary Outcome Measures: Safe dose of PRG-2311 infusion, To evaluate the safe dose of PRG-2311 infusion, 3 dosage group were designed in this trial, they are 35×10\^6 CAR-T, 100×10\^6 CAR-T, and 300×10\^6 CAR-T, Up to 24 months after PRG-2311 infusion|Occurrence of AE after PRG-2311 infusion, To evaluate the occurrence of AE after PRG-2311 infusion based on CTCAE v5.0, Up to 24 months after PRG-2311 infusion
Secondary Outcome Measures: LN: Changes of SLE disease activity Index (SLEDAI-2000) score, SLEDAI-2000 is the most commonly used SLE assessment scale. A total of 24 items, the total score is 105 points, scores ≤6 points indicates mild activity, ≥7 but ≤12 is classified as moderate activity, \>12 is classified as severe activity., Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|LN: Changes of FACIT score, FACIT score is used to assess the fatigue status of patient, Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|LN: Changes of PGA score, PGA score is used to assess the disease activity status of patient by physician, Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|LN: Changes of UPCR, UCPR: urinary protein creatinine ratio (ug/mg), Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|LN: Changes of eGFR, eGFR : estimated glomerular filtration rate (ml/min/1.73m\^2), Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|LN: overall response rate (complete or partial renal response, complete renal response rate or partial renal response rate, Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|IgG4-RD: time to disease relapse, Definition:The number of days between the date of CAR-T infusion and the date of IgG4-RD recurrence determined by a clinical professional physician during the follow-up period, Up to 24 months after PRG-2311 infusion|IgG4-RD: changes in the proportion of patients with improved disease activity (IgG4-RD RI), IgG4-RD (IgG4-RD RI) responder index is the most commonly used IgG4-RD assessment scale, Baseline,1st month, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|IgG4-RD: The annual relapse rate, The annual recurrence rate, Up to 24 months after PRG-2311 infusion|IgG4-RD: The proportion of patients achieved a complete response at week 52, The proportion of complete response, 24 months after cell infusion|PK: the feature of copy numbers of CAR-Cmax, Cmax, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PK: the feature of copy numbers of CAR-Tmax, Tmax, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PK: the feature of copy numbers of CAR-AUC0-28d, Cmax、Tmax、AUC0-28d、AUC0-90d、T last of the copy numbers of CAR, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PK: the feature of copy numbers of CAR-AUC0-90d, AUC0-90d, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PK: the feature of copy numbers of CAR-T last of the copy numbers of CAR, T last of the copy numbers of CAR, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PK: changes of the proportion of CAR-T cells to T cells, Flow cytometry is used to detect the proportion of CAR-T cells to T cells., Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, 2nd month, 3rd month|PD: changes of the levels of plasma sBCMA, IgG, IgA, IgM, complement C3 and C4, Immunology-related index, Screening period, Baseline, Day 14, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PD: changes of pathogenic antibody titers, Changes of ANA, anti-JO1, anti-SSA, anti-SSB, anti-Ro52, anti-centromerin B, anti-histone, anti-rRNP, anti-Scl70, anti smith, anti-ul-RNP and anti-dsDNA antibody titers in peripheral blood (only for enrolled lupus nephritis patients), and changes of IgG1, IgG2, IgG3, IgG4, and IgE (only for enrolled IgG4-RD patients), Screening period, Baseline, Day 14, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|PD: changes of immunoinflammation related laboratory indices, Changes of laboratory indices related to immune responses and inflammation in peripheral blood, including ESR, hsCRP, LDH, and serum cytokines, Screening period, Baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28 after cell infusion|PD: changes of T and B lymphocyte subpopulations in peripheral blood, Changes of lymphocyte subgroup in peripheral blood, Screening period, Baseline, Day 14, Day 28, 2nd month, 3rd month, 6th month, 9th month, 12th month, 18th month, and 24th month after cell infusion|BCMA expression levels of memory B cells and plasma blast cells, BCMA expression levels of memory B cells and plasma blast cells in peripheral blood, Screening period, baseline, Day 14, Day 28, month 2, month 3, month 6, month 9, month 12 and month 24|Single cell sequencing, Single cell sequencing of peripheral blood T cells, B cells and CAR-T, Screening period, 3 months after cell infusion (or B cell recovery stage), or depending on the investigator's assessment|The change of national planning vaccine antibody levels, To evaluate the effect of CAR-T clearance of B cell on immunological protection after vaccination, Screening period, 3 months after cell infusion