Lupus Nephritis, Systemic Lupus Erythematosus
Conditions
Keywords
CAR T-cell, CD19/20, CD19, CD20, Lupus Nephritis, LN, Systemic Lupus Erythematosus, SLE, Active refractory systemic lupus erythematosus, Active refractory Lupus Nephritis
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.
Interventions
BIOLOGICALIMPT-514
CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide
Sponsors
Lyell Immunopharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent 2. Age 18 years of age or older 3. Weight \> 45 kg at enrollment 4. Adequate blood pressure control 5. On stable background therapy for autoimmune disease (LN, SLE) with stable dose of autoimmune disease medications for at least 4 weeks prior to screening 6. 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 7. Positive anti-nuclear antibody (ANA), anti-dsDNA (double stranded DNA) or anti-Smith antibody at screening 8. SLE participants: SLEDAI-2K ≥ 6 points, with at least 4 points on clinical, non-laboratory items 9. 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 10. Physician Global assessment ≥ 1 on 0 to 3 visual analogue scale (VAS) 11. 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.
Exclusion criteria
1. Any clinically significant underlying illness, other than SLE and LN, which would pose a safety risk or concern, as determined by the Investigator 2. Any other systemic autoimmune condition 3. Rapidly progressive glomerulonephritis 4. Active central nervous system (CNS) lupus 5. History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation 6. 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 7. Drug-induced SLE Other protocol-defined criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Australia, United States
Outcome results
None listed