This is a single-arm, open-label，phase I clinical study to evaluate the safety and tolerability of Inaticabtagene Autoleucel Injection in treatment of refractory systemic lupus erythematosus-related immune thrombocytopenia.
Age range: 18-70 years (including 18 and 70 years), regardless of gender.
Clinically diagnosed with Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia according to the revised criteria of ACR in 1997 or EULAR/ACR in 2019. At least two consecutive blood routine tests showing platelet counts <50×10^9/L; Peripheral blood smear microscopy showed no significant abnormalities in the morphology of blood cells; The morphological characteristics of bone marrow cells are consistent with immune thrombocytopenia. Treated at least 1 course of MP shock therapy or high-dose steroids, combined with one or more immunosuppressive agents (including biologics) for at least 3 months but not achieving partial remission, or the efficacy cannot be maintained during the steroid reduction process.
During the study period, the use of corticosteroids at a dose not exceeding 10mg prednisone or its equivalent, all immunosuppressants (excluding hydroxychloroquine) should be discontinued.
Hysterectomy or oophorectomy, or
Severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accidents, or CNS vasculitis requiring therapeutic intervention within 60 days after baseline.
Dialysis patients or creatinine clearance rate less than 30mL/min.
Pregnancy or breastfeeding.
Merge active infections (such as sepsis, bacteremia, mycosis, uncontrolled lung infections, and active tuberculosis).
Single group
Inaticabtagene autoleucel Injection
DrugInaticabtagene autoleucel Injection, the autologous 2nd generation CD19-directed CAR-T cells, will be administered by vein. Before CAR-T infusion，patients will get a 3-4 days lymphodepletion therapy with fludarabine and cyclophosphamide.
Incidence of Treatment-related Adverse Events
Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
The safe dosage for a single infusion of Inaticabtagene Autoleucel Injection
The safe dosage for ITP patients will be evaluated by comprehensively assessing the Overall Response Rate (ORR) and the incidence of adverse events (AEs).
Overall Remission Rate (ORR)
The proportion of subjects achieving CR or PR after treatment by Inaticabtagene Autoleucel Injection.CR is defined as platelet count ≥100×10\^9/L. PR is defined as platelet count ≥30×10\^9/L and at least doubling from baseline, without active bleeding.
Proportion of subjects who achieved disease remission (DORIS)
The proportion of subjects to meet the following 2 criteria: 1.Clinical lupus erythematosus disease activity index (SLEDAI)=0. 2.Physician global assessment (PGA) is less than 0.5 (standard score is 0-3 points) without considering serological testing and low dose corticosteroids with a dose of ≤ 5mg/d (taking prednisone as an example) permitted. Antimalarial drugs, stable dose immunosuppressants, including biologics are allowed to be used.
Proportion of subjects who achieved lupus hypoactivity state (LLDAS)
The proportion of subjects to meet the following 5 criteria: 1. SLEDAI score ≤ 4, no activity of important organs, no hemolytic anemia or gastrointestinal activity; 2. Compared with previous assessments, there is no new lupus activity; 3. SELENA-SLEDAI physician overall assessment (PGA 0-3) ≤ 1 point; 4. The current dose of prednisone is ≤ 7.5mg/d; 5. Immunosuppressants and biologics with standard maintenance doses are well tolerated.
Improvement in systemic lupus erythematosus scores (SELENA-SLEDAI)
0 to 4 is basically no disease activity;5 to 9 is light activity;10 to 14 is moderate activity;≥15 is considered heavy activity.
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