Diffuse Cutaneous Systemic Sclerosis, Lupus Nephritis, Systemic Lupus Erythematosus, Systemic Sclerosis (SSc)
Conditions
Keywords
Chimeric antigen receptor, CAR T, Zamtocabtagene autoleucel, Autoimmune Disease, Immune System Diseases, SLE-Non renal, SLE-LN, SSc, dcSSc, Lupus
Brief summary
AID is a phase I multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (SLE-Non renal, SLE-LN, SSc/dcSSc) after receiving standard therapy.
Detailed description
This is a Phase 1, multicohort, dose-finding study evaluating autologous T cells engineered to target dual CD19 and CD20 antigens in subjects with refractory autoimmune diseases following standard therapy. The investigational product, Zamto-cel, is a chimeric antigen receptor T-cell (CAR-T) therapy genetically engineered to enable subjects' T cells to express CARs on their surfaces. Eligible subjects will undergo leukapheresis for the collection of cells required for manufacturing. Prior to infusion of the fresh CAR-T product, subjects will receive a lymphodepleting regimen consisting of cyclophosphamide and fludarabine. The CAR-T cell infusion will be administered intravenously at a dose of 2.5 x 10\^6 or 1.0 x 10\^6 CAR+ cells/kg body weight, based on the dose level assigned to the cohort. The study will initially enroll 3 subjects per cohort in a staggered manner to evaluate safety. Upon confirmation of safety, the study will proceed to cohort-specific recommended Phase 2 dose (RP2D) and dose expansion phases. Subjects will be monitored for up to 1 year to assess safety, preliminary efficacy, and health-related quality of life (HRQoL). Additional long-term follow-up will be conducted under a separate long-term follow-up protocol.
Interventions
BIOLOGICALzamtocabtagene autoleucel
chimeric antigen receptor T-cell (CAR-T) therapy
DRUGCyclophosphamide
Lymphodepleting chemotherapy
DRUGFludarabine
Lymphodepleting chemotherapy
Sponsors
Miltenyi Biomedicine GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Key Inclusion/
Exclusion criteria
Across All Cohorts Inclusion Criteria: •Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc/ dcSSc)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) | From enrollment through study completion 12 months post zamto-cel infusion |
| The proportion of subjects with dose-limiting toxicities (DLTs) up to Day 28 and determination of recommended Phase 2 dose (RP2D) | From enrollment through Day 28 post zamto-cel infusion |
Secondary
| Measure | Time frame |
|---|---|
| The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) | From enrollment through study completion 12 months post zamto-cel infusion |
| Clinical response at Week 4, 12, 24, and 52 evaluated by defined disease-specific activity measures in SLE-Non renal, SLE-LN, and SSc/dcSSc | From enrollment through study completion 12 months post zamto-cel infusion |
| The duration of remission or low disease activity status in respective diseases under the study | From enrollment through study completion 12 months post zamto-cel infusion |
| Persistence, maximal drug concentration (Cmax), time to reach Cmax, area under the concentration curve, and phenotype of zamto-cel | From enrollment through study completion 12 months post zamto-cel infusion |
Countries
United States
Contacts
CONTACTSadie Swift
CONTACTParis Jamiel
STUDY_DIRECTOREsther Eromosele, MD
Miltenyi Biomedicine
Outcome results
None listed