Overview
This is an exploratory trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of a single dose of IMPT-514, an autologous, anti-CD19/CD20 CAR T therapy, administered as an intravenous (IV) infusion, in participants with B cell driven autoimmune diseases, including active, refractory Systemic Lupus Erythematosus (SLE), ANCA Associated Vasculitis (AAV), and Idiopathic Inflammatory Myopathy (IIM).
Description
This study will explore the safety of IMPT-514 and will include up to two dose levels, with up to 12 total expected dosed participants for each disease group of SLE, AAV, and IIM.
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 2 year from IMPT-415 administration.
Eligibility
General Inclusion Criteria:
- Willing and able to provide written informed consent.
- Age 18 years of age or older and ≤75 years.
- Weight > 35 kg at enrollment.
- On stable background therapy (such as mycophenolate, cyclophosphamide, etc.) for autoimmune disease (SLE, AAV, IIM) with stable dose of immunosuppressants for at least 4 weeks prior to screening.
For SLE participants:
- Diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria or 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, including positive ANA >1:80 or positive anti-dsDNA.
For AAV participants:
- Meets the diagnostic criteria for ANCA vasculitis in 2022 ACR/EULAR, including microscopic polyangiitis (MPA), granulomatous polyangiitis (GPA), and eosinophilic granulomatous polyangiitis (EGPA).
For IIM (Dermatomyositis, Anti-Synthetase Syndrome, and Immune-Mediated Necrotizing Myopathy) participants:
- Diagnosis of probable or definite IIM with subgroup classification of dermatomyositis, or immune-mediated necrotizing myopathy (IMNM) subgroup of polymyositis.
Exclusion Criteria:
- Any clinically significant underlying illness, other than systemic autoimmune disease (SLE, AAV, IIM), which would pose a safety risk or concern, as determined by the Investigator.
- Rapidly progressive glomerulonephritis.
- For SLE participants: Active central nervous system (CNS) lupus.
- History of, or current significant neurologic disease.
- History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation (such as kidney, lung, heart transplant) or plans for such transplantation in future.
- History of prior CAR T treatment, autologous or allogeneic.
- Drug induced SLE, drug induced vasculitis or drug induced myopathy or myositis.
- Any primary immunodeficiency.
- History of, or current significant cardiovascular dysfunction.