BCMA-CD19 cCAR T for the Treatment of Refractory Lupus

Official title

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

Overview

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.

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.

Interventions

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

Primary outcome measures

• Number of Adverse Events after ICG318 infusion [Time frame: Starting day 0 and up to 1 year after ICG318 infusion.]
• DORIS remission rate [Time frame: Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.]

Secondary outcome measures (12)

• Determine the recommended phase 2 dose (RP2D) regimen. [Time frame: Starting day 0 and assessed 1 year after ICG318 infusion.]
• Cmax [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• Tmax [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• T1/2 [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• AUC [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• Rate of B cell elimination and naïve B-Cell recovery [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• Recovery of immunoglobulins [Time frame: Assessed as per schedule of events up to 1 year after ICG318 infusion.]
• SLE Autoantibody levels [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) [Time frame: Starting day 0 and assessed at 6 months, and 1 year after ICG318 infusion.]
• Renal histology [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 [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.]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07328581 · ICG318-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗