This is a Phase I, IIa, Single-Arm, interventional, open label, treatment study to evaluate the safety and tolerability of BCMA-CD19-IL-15/IL15sushi cCAR T cells in patients with relapsed and/or refractory SLE, with or without Lupus Nephritis.
Systemic Lupus Erythematosus (SLE) is a multisystem, chronic autoimmune disease that may impact multiple organs including the joints, skin, kidney, heart, brain and lungs, with severity ranging from mild to life-threatening. Lupus Nephritis (LN) is the most prevalent and severe form of SLE with high morbidity and mortality and persistent relapses despite current therapies. SLE, with or without LN is driven largely by pathogenic autoantibodies produced by CD19 expressing B cells and BCMA expressing plasma cells, including long-lived plasma cells. ICG318, the investigational agent in this clinical trial is an armored, compound chimeric antigen receptor (CAR) composed of two independently functioning CARs that simultaneously target the B-cell CD19 surface antigen and the plasma cell/ long lived plasma cell BCMA surface antigen. This study is being conducted to evaluate the safety and efficacy of ICG318 in SLE patients with or without LN, who have not shown adequate clinical response to prior therapies. A single dose of ICG318 following a cyclophosphamide-only lymphodepletion regimen will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Anti-BCMA, Anti-CD19 Compound CAR-T Cells
Number of Adverse Events after ICG318 infusion
Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESI), and Dose Limiting Toxicities (DLTs).
Time frame: Starting day 0 and up to 1 year after ICG318 infusion.
DORIS remission rate
DORIS remission defined as no circulating autoantibodies (e.g. dsDNA, Smith etc.) detected, no SLE medications, and SLEDAI-2K score of 0-1 (down from severe 7-10).
Time frame: Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.
Determine the recommended phase 2 dose (RP2D) regimen.
The protocol is based on cohort schema with dose escalation from 0.5x10\^6/kg to 4x10\^6/kg.
Time frame: Starting day 0 and assessed 1 year after ICG318 infusion.
Cmax
Maximum serum concentration of ICG318.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
Tmax
Time to maximum serum concentration of ICG318.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
T1/2
Half-life of ICG318 serum concentration.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
AUC
Plasma ICG318 concentration versus time. Total systemic exposure to ICG318 over time.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Rate of B cell elimination and naïve B-Cell recovery
B cell subsets will be assessed by flow cytometry panels and B-Cell receptor sequencing.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
Recovery of immunoglobulins
Immunoglobulins IgG, IgM and IgA levels.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
SLE Autoantibody levels
Changes in levels of SLE specific autoantibodies (e.g. dsDNA, Smith etc.)
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
Number of patients achieving DORIS remission, LLDAS, Complete or Partial Renal Response (in LN patients)
As per the DORIS and SLEDAI-2K remission criteria.
Time frame: Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.
Renal histology
Renal Biopsies will be performed prior to and post-ICG318 infusion.
Time frame: The first biopsy will be obtained prior to ICG318 infusion. Next biopsy will be assessed up to 6 months to 1 year after ICG318 infusion.
Complement levels
Changes in C3 and C4 complement levels in serum.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
Serum creatinine levels
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
Urine Protein-Creatinine Ratio (uPCR) levels.
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.
eGFR value
Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.