A Study of NKX019, a CD19 CAR NK Cell Therapy, in Subjects With Systemic Lupus Erythematosus
NCT Number: NCT06518668
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Systemic Lupus Erythematosus
Interventions: BIOLOGICAL: NKX019|DRUG: Cyclophosphamide LD
Sponsor: Columbia University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 6
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-01
Completion Date: 2040-12
Locations: Columbia University Irving Medical Center, New York, New York, 10032, United States

Summary:
Primary objective: Safety and tolerability of NKX019, administered after lymphodepletion (LD).

Secondary objectives:

* Assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN)
* Characterize pharmacokinetics (PK) of NKX019
* Characterize immunogenicity of NKX019

Primary Outcome Measures: Incidence of adverse events (AEs), This is to measure safety and tolerability of NKX019, administered after lymphodepletion (LD). Adverse events will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including dose-limiting toxicities (DLTs). A DLT is defined as an AE or clinically significant laboratory abnormality (laboratory abnormalities, including transient \[lasting \< 24 hours\] or isolated out of range values) occurring within 28 days from the first dose that is possibly attributable to NKX019., 2 years
Secondary Outcome Measures: Change from baseline of autoantibody levels, This is to measure/assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN). Anti-double-stranded DNA (anti-dsDNA) antibodies and complement levels will be assessed at Days 90, 180, 270, and 360. Change will be evaluated from baseline of autoantibody and complement assessment as follows: Autoantibodies and Complement (C3, C4) levels., Up to 2 years after NKX019 infusion|Change from baseline in hybrid SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score, This to measure/assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN). SLEDAI score (obtained by adding the individual 24 item scores) ranges from 0 to 105, where the higher the score, the greater the degree of disease activity. Score of 6 or more are consistent with therapy requirement., Up to 2 years after NKX019 infusion|Number of participants who achieved renal response, This to measure/assess clinical activity of NKX019. For subjects with LN: Assess complete renal response (CRR) and partial renal response (PRR) per European Alliance of Associations for Rheumatology (EULAR)/European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) criteria., Up to 2 years after NKX019 infusion|Maximum concentration (Cmax) of PK in peripheral blood, This is to characterize pharmacokinetics (PK) of NKX019 and evaluate PK parameters., Up to 2 years after NKX019 infusion|Number of subjects with normalized serological activity, This is to characterize immunogenicity of NKX019 and assess humoral and cellular immunogenicity over time. Subjects will be followed at 12 weeks and overtime for normalized serological activity such as:

* Autoantibodies (anti-dsDNA, ANA, and anti-Sm) present to absent
* Complement (C3, C4, and C3 AND C4) levels low to normal/high, Up to 2 years after NKX019 infusion