A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With Autoimmune Disease

Description

This is an open-label, multi-center, non-randomized Phase 1 study to determine the safety and tolerability of NKX019 (allogeneic CAR NK cells targeting CD19) in participants with active lupus nephritis (LN).This is a dose-finding study of NKX019 and will be conducted in 2 parts: Part 1 dose escalation and Part 2 dose expansion will utilize a "3+3" design. The study will evaluate safety and tolerability, preliminary activity, cellular kinetics, pharmacodynamics in participants with active LN. Participants will receive three-dose cycle of NKX019 following single-agent lymphodepletion with cyclophosphamide.

Trial Eligibility

Inclusion Criteria: 1. Age ≥18 and ≤65 2. Meets American College of Rheumatology (ACR) 2019 classification criteria for SLE 3. Active LN Class III or IV using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria (Bajema 2018) as evidenced on kidney biopsy during screening or within 6 months before study enrollment. Per NIH indices, subjects must have at least moderate activity score and no more than moderate chronicity index 4. Active renal disease as defined by urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥1.5 g/day and ≤ 7 g/day 5. Positive antinuclear antibodies (ANA) ≥ 1:80 OR anti-dsDNA OR anti-Smith (anti-Sm) 6. Refractory LN defined as having received ≥ 2 prior therapies for LN 7. Progression despite maximal tolerated doses of renin-angiotensin system (RAS) blockade agents 8. Negative SARS-CoV-2 test Exclusion Criteria: 1. eGFR ≤ 45 ml/min/m2 2. Currently requiring renal dialysis or expected to require dialysis during the study period 3. Previous solid organ or hematopoietic cell transplant or planned transplant within study treatment period 4. Congenital or acquired immunodeficiency resulting in severe infection or those receiving chronic immunoglobulin replacement therapy 5. Liver disease or dysfunction, including cirrhosis and/or aspartate aminotransferase, alanine aminotransferase, or bilirubin ≥ 3 times the upper limit of normal 6. Pulmonary comorbidity including chronic obstructive pulmonary disease or asthma requiring daily oral steroids, resting hypoxemia (\<92% oxygen saturation via pulse oximetry) on room air, or significant smoking history (i.e. \>10 pack/year) 7. White blood cell count \< 3,000/mm\^3; hemoglobin levels \< 9 gm/dL absolute neutrophil count \< 2,000/mm\^3; platelet count \< 100,000/mm\^3 8. Major cardiac disease, abnormalities, or interventions as defined by, but not limited to: 1. Uncontrolled angina or unstable life-threatening arrhythmias 2. History of myocardial infarction within 12 weeks prior to the first dose of NKX019 3. Any prior coronary artery bypass graft surgery 4. ≥ Class III New York Heart Association (NYHA) congestive heart failure (CHF), significantly decreased ejection fraction (EF ≤ 40%), or severe cardiac insufficiency. 5. Prolongation of the QT interval corrected for heart rate (QTc) (Fridericia) interval of \> 480 msec 6. Peripheral artery bypass graft surgery, pulmonary embolism, or other ≥ Grade 2 thrombotic or embolic events within 12 weeks prior to the first dose of NKX019 9. Active bleeding disorders 10. Any overlapping autoimmune condition for which the condition itself or the treatment of that condition may affect the study assessments or outcomes as well as any condition for which additional immunosuppression is indicated (e.g. scleroderma with significant pulmonary hypertension) 11. Pregnancy, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions 12. Current infection requiring active systemic anti-infective therapy or recent acute infection requiring systemic therapy within 30 days of planned LD 13. History of positive HIV antibody or test positive at screening, Hepatitis B or C positive at screening, active tuberculosis (TB) or latent TB requiring suppressive therapy 14. Known antiphospholipid antibody syndrome (APS); or high-risk profile 15. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia but have been treated with conization or loop electrosurgical excision procedure and have had a normal repeat Papanicolaou test are allowed 16. Prior cellular therapy 17. Central nervous system (CNS) comorbidity or any autoimmune disease with CNS involvement within 90 days prior to the first dose of NKX019 as well as active CNS lupus within 1 year prior to screening

Study Info

Interventions

Locations Recruiting

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