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A Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)

RecruitingPhase 1, Phase 2Ages 18 Years - 75 YearsAllNkarta, Inc.
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In plain words

What the trial is, and whether it could suit you

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.

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
General Inclusion Criteria: 1. Age ≥18 and ≤75 2. Signed informed consent form and ability to adhere to the study visit schedule and comply with other protocol requirements 3. Women of childbearing potential must have negative pregnancy tests at screening and baseline, and agree to abstinence or acceptable birth control from 2 weeks prior to the first dose through 1 year after the last dose 4. Progression despite maximal tolerated doses of renin-angiotensin system (RAS) blockade agents 5. . For participants taking chronic corticosteroids for management of the disease under study, the prednisone (or equivalent) dose must be ≤20 mg/day at 2 weeks prior to Screening and stable for ≥ 14 days before start of Screening 6. For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening LN-specific Inclusion Criteria: 1. Score of 10 or more points on the American College of Rheumatology (ACR) 2019 classification criteria for SLE 2. Active biopsy proven lupus nephritis Class III or Class IV without Class V overlap using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria as evidenced on kidney biopsy during consent or within 6 months before screening. The biopsy must have at least mild to moderate activity score and no more than moderate chronicity index per NIH indices 3. Active renal disease as defined by urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥1.5 g/day on a 24-hour collection and ≤ 7 g/day by either measure 4. One or more of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening OR positive anti-dsDNA OR positive anti-Smith (anti-Sm) 5. Refractory LN defined as having received ≥ 2 prior therapies for LN (immunosuppressant and corticosteroid/or immunomodulatory agent, and corticosteroid at therapeutic range for at least 90 days), and had an inadequate response to therapy despite being on a therapeutic dose for ≥ 90 days pMN-specific Inclusion Criteria: 1. Evidence of pMN by renal biopsy during screening or within 6 months before screening 2. Active renal disease at screening defined by spot UPCR ≥ 3.5 g/g or proteinuria ≥ 3.5 g/day on a 24-hour collection 3. Presence of primary membranous nephropathy autoantibodies 4. Refractory or intolerant to at least 1 induction therapy for pMN (immunosuppressant and corticosteroid or immunomodulatory agent and/corticosteroid) and defined as not achieving a complete remission after 180 days, or partial remission after 90 days General Exclusion Criteria: 1. eGFR \< 45 ml/min/1.73 m\^2 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) with active pulmonary disease 7. Bone marrow insufficiency unrelated to active underlying autoimmune disease with white blood cell count \< 3,000/mm\^3; hemoglobin levels \< 9 gm/dL absolute neutrophil count \< 1500/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 7. Uncontrolled hypertension (systolic BP \> 160mmHg and/or diastolic BP \> 90mmHg) despite therapy 9. Active bleeding disorders 10. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (eg, anti-GBM antibody glomerulonephritis or any condition for additional immunosuppression is indicated); clinically significant conditions that could cause a secondary nephropathy (eg, infections, liver disease, tumors or drugs); or kidney biopsy-confirmed significant renal disease other than disease under study (eg, diabetic nephropathy, hypertensive nephropathy). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (eg, Sjögren's syndrome, rheumatoid arthritis) are not excluded 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. Major surgery within 28 days prior to the first dose of NKX019 or any surgery from which the participant has not recovered or has ongoing complications 15. Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Participants with cervical dysplasia that is cervical intraepithelial neoplasia
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What it tests

  • NKX019
  • Fludarabine, Cyclophosphamide
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Where

19 sites
Nkarta Investigational Site
Little Rock, United States
Nkarta Investigational Site
Tustin, United States
Nkarta Investigational Site
Gainesville, United States
Nkarta Investigational Site
Miami, United States
Nkarta Investigational Site
Plantation, United States
Nkarta Investigational Site
Tampa, United States
Nkarta Investigational Site
Atlanta, United States
Nkarta Investigational Site
Chicago, United States

…and 11 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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