This is a Phase 1/2, open-label, multi-center, multi-cohort, non-randomized dose escalation and dose expansion basket study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting CD19) in participants with autoimmune diseases.
Dose escalation of NKX019 will utilize a "3+3" design to determine the recommended dose(s) for enrolling additional participants across indications. The study will evaluate safety and tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics in participants with autoimmune diseases. Participants will receive a cycle consisting of lymphodepletion with fludarabine and cyclophosphamide (Flu/Cy), followed by three doses of NKX019. Participants who are cytopenic may receive a modified LD regimen of Cy alone.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
120
NKX019 is an investigational allogeneic CD19-Directed CAR NK
For Lymphodepletion
Nkarta Investigational Site
Little Rock, Arkansas, United States
RECRUITINGIncidence of dose-limiting toxicities (DLTs) [Safety and Tolerability]
Incidence of DLTs will be evaluated
Time frame: The first 28 days after the first NKX019 dose
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence and severity of treatment-emergent adverse events will be evaluated
Time frame: From the first administration of NKX019 until the last administration of any study treatment + 30 days
Incidence of clinically significant abnormalities in clinical laboratory assessments [Safety and Tolerability]
Incidence of clinically significant laboratory abnormalities will be evaluated
Time frame: From the first NKX019 dose until the last follow up visit
LN only: Number of participants who achieved Primary Efficacy Renal Response (PERR), complete renal response (CRR) and partial renal response (PRR)
Primary Efficacy Renal Response (PERR), complete renal response (CRR) and partial renal response (PRR) to treatment will be assessed based on European Alliance of Associations for Rheumatology (EULAR)/European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) criteria
Time frame: Up to 2 years after NKX019 infusion
LN only: Assessment of Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) remission over time
Time frame: Up to 2 years from NKX019 infusion
LN only: Change from baseline in Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) score over time
The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity
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Nkarta Investigational Site
Tustin, California, United States
RECRUITINGNkarta Investigational Site
Gainesville, Florida, United States
RECRUITINGNkarta Investigational Site
Miami, Florida, United States
WITHDRAWNNkarta Investigational Site
Plantation, Florida, United States
RECRUITINGNkarta Investigational Site
Tampa, Florida, United States
RECRUITINGNkarta Investigational Site
Atlanta, Georgia, United States
RECRUITINGNkarta Investigational Site
Chicago, Illinois, United States
RECRUITINGNkarta Investigational Site
New Orleans, Louisiana, United States
RECRUITINGNkarta Investigational Site
Worcester, Massachusetts, United States
RECRUITING...and 9 more locations
Time frame: Up to 2 years from NKX019 infusion
pMN only: Number of participants who achieved complete remission (CR) and partial remission (PR) and their components (Couser 2017)
Time frame: Up to 2 years from NKX019 infusion
pMN only: Change from baseline in serum albumin
Time frame: Up to 2 years after NKX019 infusion
pMN only: % change from baseline in estimated glomerular filtration rate (eGFR)
Time frame: Up to 2 years after NKX019 infusion
Maximum Concentration (Cmax) of NKX019 in peripheral blood
Time frame: Up to 2 years after NKX019 infusion
Time to Cmax (Tmax) of NKX019 in peripheral blood
Time frame: Up to 2 years after NKX019 infusion
Area Under the Concentration-time Curve (AUC) of NKX019 in peripheral blood
Time frame: Up to 2 years after NKX019 infusion
Half-life (t1/2) of NKX019 in peripheral blood
Time frame: Up to 2 years after NKX019 infusion
Duration of Persistence of NKX019 in peripheral blood
Time frame: Up to 2 years after NKX019 infusion
Assess humoral and cellular immunogenicity over time with validated methods that include: a cell-based flow cytometry assay for anti-NKX019 antibodies and an antigen bead-assay using flow cytometry for detection of anti-HLA antibodies
Time frame: Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies
Proportion of subjects requiring rescue therapy over time
Time frame: Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies
Proportion of subjects who are steroid free over time
Time frame: Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies
Cumulative corticosteroid dose over time
Time frame: Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies
Proportion of subjects receiving ≤5 mg daily prednisone (or equivalent) over time
Time frame: Up to 2 years after NKX019 infusion
Evaluation of the effect of treatment on background therapies
Proportion of subjects receiving ≤7.5 mg daily prednisone (or equivalent) over time
Time frame: Up to 2 years after NKX019 infusion