BCMA-CD19 cCAR T for the Treatment of Refractory Lupus

Phase I, IIa, Single-Arm, Study of BCMA-CD19-IL-15/IL15sushi cCAR T for the Treatment of Refractory Systemic Lupus Erythematosus, With or Without Lupus Nephritis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus (SLE); Lupus Nephritis (LN)
• Intervention / Treatment: Biological: ICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR T following cyclophosphamide-only lymphodepletion

Detailed Description

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
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Kevin Pinz, MS; Phone Number: 6315386218; Email: kevin.pinz@icellgene.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Age 16-70 years at the time of signing the informed consent
2. Have a diagnosis of SLE by EULAR/ACR 2019 criteria for ≥6 months.
3. Have at least one of an antinuclear antibody, anti-double-stranded deoxyribonucleic acid (dsDNA), or elevated anti-Smith (Sm) antibody
4. Inadequate response to 2 prior standard of care therapies, used for at least three months
5. SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥7 at Screening
6. For LN cohort participants. Kidney biopsy result within 6 months prior to Screening indicating Class III or IV (alone or in combination with Class V)6.

Key Exclusion Criteria:

1. Any acute, severe lupus related flare that needs immediate treatment
2. History of antiphospholipid syndrome with thromboembolic event within 12 months
3. History or current diagnosis of any disease, condition or treatment that may confound clinical assessments in the study.
4. Has drug-induced SLE.
5. History of prior CAR-T therapy.
6. History of bone marrow/hematopoietic stem cell or solid organ transplant or planned receipt during the study period.
7. Recent serious or ongoing infection, or risk for serious infection, or acute or chronic infection
8. Receipt of a live/live-attenuated vaccine other than BCG within 8 weeks
9. History within the past year or current clinically significant central nervous system disease, including but not limited to cerebrovascular accident, seizures, severe brain injury, dementia, Parkinson's disease, cerebellar disease, or multiple sclerosis
10. Impaired cardiac function or clinically significant cardiac disease
11. End stage renal disease or severe liver disease
12. Breastfeeding/lactating or pregnant women or women who intend to become pregnant at any time during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; Biologic drug infusion	Biological: ICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR T following cyclophosphamide-only lymphodepletion; Anti-BCMA, Anti-CD19 Compound CAR-T Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Starting day 0 and assessed 1 year after ICG318 infusion.
Cmax	Maximum serum concentration of ICG318.	Assessed as per schedule of events up to 1 year after ICG318 infusion.
Tmax	Time to maximum serum concentration of ICG318.	Assessed as per schedule of events up to 1 year after ICG318 infusion.
T1/2	Half-life of ICG318 serum concentration.	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.	Assessed as per schedule of events up to 1 year after ICG318 infusion.
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.	Assessed as per schedule of events up to 1 year after ICG318 infusion.
Recovery of immunoglobulins	Immunoglobulins IgG, IgM and IgA levels.	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.)	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.	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.	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.	Assessed as per schedule of events up to 1 year after ICG318 infusion.
Serum creatinine levels		Assessed as per schedule of events up to 1 year after ICG318 infusion.
Urine Protein-Creatinine Ratio (uPCR) levels.		Assessed as per schedule of events up to 1 year after ICG318 infusion.
eGFR value		Assessed as per schedule of events up to 1 year after ICG318 infusion.

Collaborators and Investigators

• Sponsor: iCell Gene Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 17, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Lupus; CAR-T Cell; CD19; autoimmune disease; BCMA; Lupus Nephritis (LN); Refractory disease; Systemic Lupus Erythrematosus (SLE)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Disease; Lupus Nephritis; Autoimmune Diseases
• Other Study ID Numbers: ICG318-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No