BCMA-CD19 cCAR T for the Treatment of Refractory Lupus

iCell Gene Therapeutics

Status and phase

Not yet enrolling

Phase 2

Phase 1

Conditions

Lupus Nephritis (LN)

Systemic Lupus Erythematosus (SLE)

Treatments

Biological: ICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR T following cyclophosphamide-only lymphodepletion

Study type

Interventional

Funder types

Industry

Identifiers

NCT07328581

ICG318-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

16 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Age 16-70 years at the time of signing the informed consent
Have a diagnosis of SLE by EULAR/ACR 2019 criteria for ≥6 months.
Have at least one of an antinuclear antibody, anti-double-stranded deoxyribonucleic acid (dsDNA), or elevated anti-Smith (Sm) antibody
Inadequate response to 2 prior standard of care therapies, used for at least three months
SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥7 at Screening
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:

Any acute, severe lupus related flare that needs immediate treatment
History of antiphospholipid syndrome with thromboembolic event within 12 months
History or current diagnosis of any disease, condition or treatment that may confound clinical assessments in the study.
Has drug-induced SLE.
History of prior CAR-T therapy.
History of bone marrow/hematopoietic stem cell or solid organ transplant or planned receipt during the study period.
Recent serious or ongoing infection, or risk for serious infection, or acute or chronic infection
Receipt of a live/live-attenuated vaccine other than BCG within 8 weeks
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
Impaired cardiac function or clinically significant cardiac disease
End stage renal disease or severe liver disease
Breastfeeding/lactating or pregnant women or women who intend to become pregnant at any time during the study.