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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of IMPT-514 in Participants With Active, Refractory Lupus Nephritis and Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus, Lupus Nephritis

Intervention / Treatment
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* Biological: IMPT-514
* Biological: IMPT-514
* Biological: IMPT-514


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent Age 18 years of age or older Weight > 45 kg at enrollment Adequate blood pressure control 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 LN participants: Active, biopsy-proven, proliferative lupus nephritis Class III or IV by 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria Other protocol-defined criteria apply. Exclusion criteria: 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 Other protocol-defined criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Lupus Nephritis<br>Administration of IMPT-514 | Biological: IMPT-514<br>* CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide<br>|
| Experimental: Phase 2 Lupus Nephritis<br>Administration of IMPT-514 | Biological: IMPT-514<br>* CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide<br>|
| Experimental: Phase 2 SLE without Lupus Nephritis<br>Administration of IMPT-514 | Biological: IMPT-514<br>* CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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: 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: Proportion of participants achieving DORIS remission at Month 6. |  | Baseline to Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LN, Systemic Lupus Erythematosus, SLE, Active refractory systemic lupus erythematosus, Active refractory Lupus Nephritis, CAR T-cell, CD19/20, CD19, CD20, Lupus Nephritis