The goal of this clinical trial is to test ATHENA CAR-T injection in adults with moderate to severe Systemic Lupus Erythematosus. The main question it aims to answer is: • To evaluate the safety and tolerability of ATHENA CAR-T. After screening, participants will be subjected to lymphodepletion regimen. After recovery, participants will be injected with ATHENA CAR-T injection and followed up to 24 months.
This study is a single center, one-arm, open label, phase I study aimed at evaluate the safety and effectiveness of ATHENA CAR-T treating moderate to severe SLE patients. A traditional "3+3" design is used with two doses. DLT is monitored. Safety and effectiveness are followed up until 24 months post infusion of ATHENA CAR-T. Besides safety monitoring, efficacy is evaluated via SLEDAI-2000, BILAG-2004, PGA.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Phase 1 dose escalation (3+3): dose 1 and dose 2.
Intravenous injection of fludarabine.
Intravenous injection of cyclophosphamide.
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, China
Dose Limiting Toxicity
Dose Limiting Toxicity (DLT) is defined as AEs related to ATHENA CART from infusion till 28 days post infusion.
Time frame: 0~28 day after treatment
Frequency of AEs, SAEs, lab abnormalities, AESIs
Monitor grade and frequency of Adverse Events (AEs), Severe Adverse Events (SAEs), abnormal laboratory findings and Adverse Events of Special Interest (AESI).
Time frame: 0 day to 24 months after treatment
Efficacy: Percent of patients achieved SRI-4
Measure percentage of patients who achieved SRI-4 (Systemic Lupus Erythematosus Responder Index-4) at week 4,8,12,16. SRI-4 response is achieved if SLEDAI-2000 score is lowered NLT 4pt compared to baseline, BILAG-2004 has no new A grade or NMT 1 new B grade, and PGA is not worsen (increase LT 0.3 compare to baseline).
Time frame: 0 to 16 weeks after treatment
Efficacy: Patients SLEDAI-2000 change compared with baseline
Compare patients' SLEDAI-2000 (Systemic Lupus Erythematosus Disease Activity Index 2000) value at baseline and week 4,8,12,16. SLEDAI-2000 is an index of range 0 to 105. Higher score indicates stronger disease activity, a score NLT 15 means strong SLE activity.
Time frame: 0 to 16 weeks after treatment
Efficacy: Patients BILAG-2004 change compared with baseline
Compare patients' BILAG-2004 (British Isles Lupus Assessment Group index 2004) value at baseline and week 4,8,12,16. Each organ system is graded from A to E, A indicate high disease activity while grade E indicate no disease activity now and then. A is assigned 9 points and E is assigned 0 points.
Time frame: 0 to 16 weeks after treatment
Efficacy: Percent of patients' PGA not worsen
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Measure percentage of patients whose PGA (Physician Global Assessment) is not worsen (increase LT 0.3 compare to baseline) at week 4,8,12,16. PGA is ranged 0 to 3, score 0 means no disease activity while score 3 means strong disease activity.
Time frame: 0 to 16 weeks after treatment
Percent of patients responded by BILAG-2004
Measure percentage of patients who responded by BILAG-2004 (no new A grade or NMT 1 new B grade) at week 4,8,12,16.
Time frame: 0 to 16 weeks after treatment
Efficacy: Immunologic parameters
Evaluate the change of immunological parameters. Including of concentration of IgG, IgA, IgM, C3, C4, unit g/L.
Time frame: 0 day to 24 months after treatment
Efficacy: Immunologic parameters (cont)
Evaluate the change of immunological parameters. Including concentration of anti-dsDNA antibody, unit IU/ml.
Time frame: 0 day to 24 months after treatment