A Study of IMPT-514 in Active Refractory Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE)

NCT06153095 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: MPCT-021N
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with active, refractory lupus nephritis and systemic lupus erythematosus. IMPT-514 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Individual participants will remain in the active post-treatment period for approximately 1 year. Participants will continue in long-term follow-up for 15 years from treatment.

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Keywords

CAR T-cell; CD19/20; CD19; CD20; Lupus Nephritis; LN; Systemic Lupus Erythematosus; SLE; Active refractory systemic lupus erythematosus; Active refractory Lupus Nephritis

Outcome Measures

Primary Outcomes (4)

• Phase I: Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other treatment-emergent adverse events (TEAEs).

  Baseline to Month 6

• Phase I: Incidence of TEAEs, percent reduction in peripheral B cells, and the proportion of enrolled participants who receive the target dose.

  Baseline to Month 6

• Phase II: Cohort 1 (LN): Proportion of participants with Complete Renal Response (CRR) as defined by EULAR/ERA-EDTA at Month 6.

  Baseline to Month 6

• Phase II: Cohort 2 (SLE): Proportion of participants achieving definition of remission in SLE (DORIS) at Month 6.

  Baseline to Month 6

Study Arms (3)

Phase 1 Lupus Nephritis

EXPERIMENTAL

Administration of IMPT-514

Biological: IMPT-514

Phase 2 Lupus Nephritis

EXPERIMENTAL

Administration of IMPT-514

Biological: IMPT-514

Phase 2 SLE without Lupus Nephritis

EXPERIMENTAL

Administration of IMPT-514

Biological: IMPT-514

Interventions

IMPT-514 BIOLOGICAL

CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide

Phase 1 Lupus Nephritis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Age 18 years of age or older
• Weight \> 45 kg at enrollment
• Adequate blood pressure control
• On stable background therapy for autoimmune disease (LN, SLE) with stable dose of autoimmune disease medications for at least 4 weeks prior to screening
• Diagnosis of SLE by 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria or 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, including positive ANA or positive anti-dsDNA
• Positive anti-nuclear antibody (ANA), anti-dsDNA (double stranded DNA) or anti-Smith antibody at screening
• SLE participants: SLEDAI-2K ≥ 6 points, with at least 4 points on clinical, non-laboratory items
• SLE participants: British Isles Lupus Assessment Group (BILAG) 2004 level B in 2 or more organ systems, or BILAG level A in 1 or more organ system
• Physician Global assessment ≥ 1 on 0 to 3 visual analogue scale (VAS)
• LN participants: Active, biopsy-proven, proliferative LN Class III or IV by 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
• Other protocol-defined criteria apply.

You may not qualify if:

• Any clinically significant underlying illness, other than SLE and LN, which would pose a safety risk or concern, as determined by the Investigator
• Any other systemic autoimmune condition
• Rapidly progressive glomerulonephritis
• Active central nervous system (CNS) lupus
• History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation
• History of prior B cell directed cell therapy, including CAR T treatment, autologous or allogeneic, as well as prior bispecific or T cell engager therapy
• Drug-induced SLE
• Other protocol-defined criteria apply.

Sponsors & Collaborators

• Lyell Immunopharma, Inc.: lead

Study Sites (4)

University of California, Los Angeles (UCLA) Medical Center

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Westmead Hospital

Westmead, NSW 2145, Australia

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 1, 2023
• Study Start: February 15, 2024
• Primary Completion: January 9, 2025
• Study Completion: January 9, 2025
• Last Updated: February 10, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); US (3)