A Phase IIa Study of ICG318 CAR-T in Refractory Systemic Lupus Erythematosus With or Without Lupus Nephritis

Phase 2RecruitingNCT07328581

iCell Gene Therapeutics20 enrolled

Overview

This Phase IIa, open-label, single-arm study includes an initial Safety Run-In followed by dose expansion to evaluate the safety, tolerability, cellular kinetics, pharmacodynamics, and preliminary clinical activity of a single infusion of ICG318 in participants with refractory SLE, with or without LN. Participants will receive protocol-specified lymphodepletion followed by ICG318 at the recommended Phase 2 dose.

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 lymphodepletion regimen will be evaluated.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 16 YearsMax age: 70 Years

Medical Language ↔ Plain English

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). 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.

Locations (4)

University of Chicago

Chicago, Illinois, United States

NOT_YET_RECRUITING

New York Medical College

Hawthorne, New York, United States

NOT_YET_RECRUITING

NorthWell

New Hyde Park, New York, United States

RECRUITING

Fox Chase Cancer Center- Temple BMT

Philadelphia, Pennsylvania, United States

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

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.

Secondary Outcomes

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.

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.

A Phase IIa Study of ICG318 CAR-T in Refractory Systemic Lupus Erythematosus With or Without Lupus Nephritis

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts