A Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)
A Phase 1/2 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With Autoimmune Disease
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 75 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests the safety of NKX019, a treatment made from donor immune cells changed to target a protein called CD19. It is for adults ages 18 to 75 with autoimmune diseases, in which the immune system attacks the body. The listed groups have lupus nephritis or primary membranous nephropathy, two diseases that harm the kidneys.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be 18 to 75, sign a consent form, and be able to follow the study schedule and rules.
- If you can become pregnant, have negative pregnancy tests. Avoid sex or use accepted birth control from 2 weeks before the first dose until 1 year after the last dose.
- Have disease that keeps getting worse despite the highest dose you can tolerate of RAS blockers, medicines used to protect the kidneys.
- If taking daily steroids, take no more than 20 mg of prednisone or an equal dose of another steroid. The dose must meet the study’s timing and stability rules.
- If taking other medicines that lower or change immune activity, keep doses stable for at least 4 weeks before screening.
- For lupus nephritis: meet the lupus scoring rules and have a recent kidney tissue test showing active class III or IV disease, without class V. Tissue damage must fall within the study’s limits.
- For lupus nephritis: meet urine protein and antibody blood test rules, and have had a poor response to at least 2 past treatments given at treatment doses for at least 90 days.
- For primary membranous nephropathy: have a recent kidney tissue test, high urine protein, and disease-related antibodies. At least 1 starting treatment must have failed under the study’s rules or caused side effects you could not tolerate.
Who can't join
- Kidney filtering level below 45, dialysis now or expected during the study, or a past organ or blood-forming cell transplant or one planned during treatment.
- Certain serious liver, lung, heart, blood, or bleeding problems; or an immune weakness that causes severe infections or needs ongoing antibody replacement treatment.
- Other autoimmune or kidney conditions that could affect study results. For lupus nephritis, active antiphospholipid antibody syndrome, a blood-clotting condition, or a high-risk profile for it also excludes you.
- Pregnancy, breastfeeding, or not using adequate birth control if you can become pregnant.
- An infection needing treatment throughout the body, or a recent infection treated this way within the study’s 30-day window; HIV, hepatitis B or C, or certain forms of tuberculosis.
- Major surgery within 28 days before treatment, incomplete recovery from surgery, or cancer within 5 years, with exceptions for certain fully removed skin cancers and treated abnormal cervical cells.
- Past cell therapy; certain brain or spinal cord conditions within 90 days before treatment; or active lupus affecting the brain or spinal cord within the past year.
- Another treatment trial without the required waiting period, medicines not allowed by this study, an allergy or other reason you cannot receive study treatment, or another health problem the study doctor believes would interfere.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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 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 including mesenchymal, CAR-T or CAR-NK cells 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 18. Any other acute or chronic medical or psychiatric condition, or known laboratory abnormality that, in the Investigator's opinion, is expected to interfere or impact study participation 19. Current participation in another interventional clinical trial a. Potential participants can be considered for enrollment after investigational product washout period of 5 half-lives or 30 days, whichever is longer 20. Currently taking or known need for any of the medications prohibited in the study protocol 21. Known hypersensitivity or contraindications to the study treatment including LD; or other components such as human serum albumin or dimethyl sulfoxide LN-specific Exclusion Criteria: 1\. Known clinically active antiphospholipid antibody syndrome (APS); or high-risk profile
Study sites (17)
AR
- Nkarta Investigational Site · Little Rock, AR 72201Nkarta Central Contact · Study contactMore trials in Little Rock
CA
- Nkarta Investigational Site · Tustin, CA 92780Nkarta Central Contact · Study contactMore trials in Tustin
FL
- Nkarta Investigational Site · Gainesville, FL 32601Nkarta Central Contact · Study contactMore trials in Gainesville
- Nkarta Investigational Site · Miami, FL 33133More trials in Miami
- Nkarta Investigational Site · Plantation, FL 33317Nkarta Central Contact · Study contactMore trials in Plantation
- Nkarta Investigational Site · Tampa, FL 33602Nkarta Central Contact · Study contactMore trials in Tampa
GA
- Nkarta Investigational Site · Atlanta, GA 30303Nkarta Central Contact · Study contactMore trials in Atlanta
IL
- Nkarta Investigational Site · Chicago, IL 60612Nkarta Central Contact · Study contactMore trials in Chicago
LA
- Nkarta Investigational Site · New Orleans, LA 70112Nkarta Central Contact · Study contactMore trials in New Orleans
MA
- Nkarta Investigational Site · Worcester, MA 01608Nkarta Central Contact · Study contactMore trials in Worcester
MI
- Nkarta Investigational Site · Ann Arbor, MI 48109Nkarta Central Contact · Study contactMore trials in Ann Arbor
NJ
- Nkarta Investigational Site · Summit, NJ 07901Nkarta Central Contact · Study contactMore trials in Summit
NY
- Nkarta Investigational Site · New York, NY 10007Nkarta Central Contact · Study contactMore trials in New York
- Nkarta Investigational Site · Stony Brook, NY 11794Nkarta Central Contact · Study contactMore trials in Stony Brook
- Nkarta Investigational Site · Syracuse, NY 13202Nkarta Central Contact · Study contactMore trials in Syracuse
TX
- Nkarta Investigational Site · Dallas, TX 75201Nkarta Central Contact · Study contactMore trials in Dallas
- Nkarta Investigational Site · Houston, TX 77002Nkarta Central Contact · Study contactMore trials in Houston